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Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Gemcitabine and Carboplatin in Metastatic Triple Negative Breast Cancer (mTNBC)

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ClinicalTrials.gov Identifier: NCT02978716
Recruitment Status : Terminated (Primary Analysis and survival follow up completed per protocol. Not stopped due to safety concerns)
First Posted : December 1, 2016
Results First Posted : March 23, 2022
Last Update Posted : March 23, 2022
Sponsor:
Information provided by (Responsible Party):
G1 Therapeutics, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Triple-Negative Breast Neoplasms
Breast Neoplasm
Breast Cancer
Triple-Negative Breast Cancer
Interventions Drug: Trilaciclib
Drug: Gemcitabine
Drug: Carboplatin
Enrollment 102
Recruitment Details This study was conducted at 34 sites in the United States (US), Belgium, Bulgaria, Croatia, Republic of Macedonia, and Serbia from 02 February 2017 (first participant enrolled) to 28 February 2020 (last participant last visit).
Pre-assignment Details Participants were screened within 28 days before the first dose of the treatment. Informed consent was obtained up to 28 days prior to first study drug administration. For tumor assessment, all sites of disease were assessed radiologically at screening. A total of 102 participants were randomized in this study.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description Participants received Intravenous (IV) infusion of standard GC chemotherapy (gemcitabine 1000 milligrams per meter square [mg/m^2] and carboplatin area under the curve [AUC] 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg). Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy. Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Period Title: Overall Study
Started 34 33 35
ITT Population [1] 34 33 35
Safety Analysis Set [2] 30 33 35
Treated 30 33 35
Completed 0 0 0
Not Completed 34 33 35
Reason Not Completed
Death             25             13             20
Lost to Follow-up             0             0             1
Withdrawal by Subject             6             4             5
Sponsor terminated             2             13             9
Other             1             3             0
[1]
The Intent-to-Treat (ITT) analysis set included all randomized participants.
[2]
The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9) Total
Hide Arm/Group Description Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg). Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy. Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy. Total of all reporting groups
Overall Number of Baseline Participants 34 33 35 102
Hide Baseline Analysis Population Description
The ITT analysis set included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 34 participants 33 participants 35 participants 102 participants
55  (13.6) 56  (12.1) 58  (9.5) 56  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 33 participants 35 participants 102 participants
Female
34
 100.0%
32
  97.0%
35
 100.0%
101
  99.0%
Male
0
   0.0%
1
   3.0%
0
   0.0%
1
   1.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 33 participants 35 participants 102 participants
Hispanic or Latino
2
   5.9%
5
  15.2%
2
   5.7%
9
   8.8%
Not Hispanic or Latino
32
  94.1%
28
  84.8%
33
  94.3%
93
  91.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 33 participants 35 participants 102 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
2
   6.1%
4
  11.4%
6
   5.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
5
  14.7%
7
  21.2%
2
   5.7%
14
  13.7%
White
28
  82.4%
22
  66.7%
28
  80.0%
78
  76.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   2.9%
2
   6.1%
1
   2.9%
4
   3.9%
1.Primary Outcome
Title Duration of Severe (Grade 4) Neutropenia (DSN) During Cycle 1
Hide Description DSN was defined as the number of days from the date of the first absolute neutrophil count (ANC) value of less than (<) 0.5 × 10^9 cells/liter (L) observed between Day 1 Cycle 1 and the end of Cycle 1 to the date of the first ANC value greater than or equal to (>=) 0.5 × 10^9/L that met the following: (1) occurred after the ANC value of < 0.5 × 10^9 cells/L and (2) no other ANC values < 0.5 × 10^9 cells/L occurred between this day and the end of Cycle 1. Severe neutropenia (SN) was set to zero for participants who did not experience severe (Grade 4) neutropenia in Cycle 1, including those who were randomized but never treated.
Time Frame From randomization to the end of Cycle 1 (Each cycle= 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Mean (Standard Deviation)
Unit of Measure: days
1  (2.2) 2  (3.5) 1  (2.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Comments Duration of SN in Cycle 1 in Group 3 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7048
Comments A Hochberg-based gatekeeping procedure was used to control the global family-wise error rate across the multiple null hypotheses in the strong sense at a 1-sided 0.025 level.
Method Analysis of covariance (ANCOVA)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.8 to 1.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.58
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
Comments Duration of SN in Cycle 1 in Group 2 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3364
Comments 2-sided p-value was calculated using a ANCOVA with study baseline ANC value as covariate, stratification factors of lines of systemic therapy, liver involvement and treatment as fixed effects.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean difference
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-0.6 to 2.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.71
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Participants With Severe (Grade 4) Neutropenia (SN)
Hide Description Number of participants with Grade 4 SN was a binary variable. If a participants had at least 1 ANC value < 0.5 ×10^9/L during the treatment period, the participants was assigned as "yes" to the occurrence of SN. Otherwise, it was "no".
Time Frame During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 4 neutropenia: Yes
9
  26.5%
12
  36.4%
8
  22.9%
Grade 4 neutropenia: No
25
  73.5%
21
  63.6%
27
  77.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Comments Number of participants with SN in Group 3 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7048
Comments A 1-sided p-value was calculated using Hochberg-based gatekeeping procedure to control the global familywise error rate across the multiple null hypotheses.
Method Modified Poisson method
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted rate ratio
Estimated Value 0.776
Confidence Interval (2-Sided) 95%
0.386 to 1.559
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2762
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
Comments Number of participants with SN in Group 2 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9154
Comments The p-value was calculated using modified Poisson method adjusting for number of cycles, accounting for the number of prior lines of therapy (0 versus 1 - 2) and liver involvement as the stratification factors and baseline ANC as a covariate.
Method Modified Poisson Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted rate ratio
Estimated Value 0.961
Confidence Interval (2-Sided) 95%
0.457 to 2.019
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.3640
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Hide Description BOR was defined as the best response across all time points (RECIST v1.1). The best overall response was determined once all the data for the participant is known. Each participant has been assigned one of the following categories (RECIST 1.1): complete response (CR): disappearance of all target lesions; partial response (PR): >= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; progression disease (PD): >= 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study); stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD); NE: not evaluable and missing.
Time Frame From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days
Hide Outcome Measure Data
Hide Analysis Population Description
The response-evaluable (RE) analysis set included all participants who were in the modified intent-to-treat (mITT) analysis set, had measurable disease (target lesions [TLs]) at the baseline tumor assessment, and had (1) at least 1 post-baseline tumor assessment, (2) clinical progression (as noted by the investigator) before their first post-baseline tumor scan, or (3) died due to disease progression before their first post-baseline tumor scan.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 24 30 31
Measure Type: Count of Participants
Unit of Measure: Participants
Complete response (CR)
0
   0.0%
0
   0.0%
0
   0.0%
Partial response (PR)
7
  29.2%
15
  50.0%
11
  35.5%
Stable disease (SD)
11
  45.8%
9
  30.0%
15
  48.4%
Progressive disease (PD)
6
  25.0%
5
  16.7%
3
   9.7%
Not evaluable (NE)
0
   0.0%
0
   0.0%
1
   3.2%
Missing
0
   0.0%
1
   3.3%
1
   3.2%
4.Secondary Outcome
Title Duration of Objective Response (DOR) as Per RECIST v1.1 as Determined by Investigator
Hide Description DOR is the time between first response by RECIST Version 1.1 of CR or PR and the first date that progressive disease is documented by RECIST Version 1.1, or death. Participants who do not experience PD or death was censored at the last tumor assessment date. 95% Confidence Interval (CI) was calculated using the Kaplan-Meier method.
Time Frame From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days
Hide Outcome Measure Data
Hide Analysis Population Description
The RE analysis set included all participants who were in the mITT analysis set, had measurable disease TLs at the baseline tumor assessment, and had (1) at least 1 post-baseline tumor assessment, (2) clinical progression (as noted by the investigator) before their first post-baseline tumor scan, or (3) died due to disease progression before their first post-baseline tumor scan. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 7 15 11
Median (95% Confidence Interval)
Unit of Measure: months
7.8 [1] 
(7.5 to NA)
11.5
(4.8 to 17.8)
9.6
(3.1 to 12.6)
[1]
Due to small number of events, estimates (upper limit of 95% Confidence interval) from Kaplan-Meier survival curves could not be derived.
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival was defined as the time (months) from date of randomization to the date of death due to any cause. Participants who do not die during the study were censored at the date last known to be alive. The OS was calculated using Kaplan-Meier method.
Time Frame From date of randomization to date of death due to any cause, assessed up to a maximum of 1120 days
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Median (95% Confidence Interval)
Unit of Measure: months
12.6
(6.3 to 15.6)
NA [1] 
(10.2 to NA)
17.8
(12.9 to 32.7)
[1]
Data could not be estimated due to higher number (>50%) of censored participants.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Comments Overall survival in Group 3 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments P-value was calculated using the stratified log-rank test to account for the number of prior lines of therapy (0 versus 1 - 2) and liver involvement as the stratification factors.
Method stratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted hazard ratio (HR)
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.22 to 0.74
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.125
Estimation Comments Cox regression model.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
Comments Overall survival in Group 2 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments P-value was calculated using the stratified log-rank test to account for the number of prior lines of therapy (0 versus 1 - 2) and liver involvement as the stratification factors.
Method stratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted HR
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
0.15 to 0.63
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.111
Estimation Comments Cox regression model.
6.Secondary Outcome
Title Progression Free Survival (PFS) as Per RECIST v1.1 as Determined by Investigator
Hide Description PFS was defined as the time (months) from date of randomization until date of documented PD or death due to any cause, whichever comes first. PD: >= 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study). The PFS was calculated using Kaplan-Meier method.
Time Frame From date of randomization until the occurrence of disease progression, death due to any cause or a censoring event, assessed up to a maximum of 875 days
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Median (95% Confidence Interval)
Unit of Measure: months
5.7
(3.3 to 9.2)
9.4
(6.1 to 11.9)
7.3
(6.2 to 13.9)
7.Secondary Outcome
Title Relative Dose Intensity of Gemcitabine and Carboplatin
Hide Description Relative dose intensity was defined as 100% times the actual dose intensity divided by the planned dose intensity. The planned dose intensity was defined as the cumulative planned dose through the study divided by (number of cycles × 3 weeks). Relative dose intensity (%) was calculated as: for gemcitabine (100 * [Dose intensity (mg/m2/week) / (2000/3 (mg/m2/week)]); for carboplatin (100 * [Dose intensity (AUC/week)/ (4/3) (AUC/week)]) and for trilaciclib (100 * [Dose intensity (mg/m2/week)/ (480 /3 (mg/m2/week)] for Group 2 and 100 * [Dose intensity (mg/m2/week) / (960 /3 (mg/m2/week)] for Group 3).
Time Frame During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 30 33 35
Mean (Standard Deviation)
Unit of Measure: percentage of dose
Carboplatin 77.5  (19.20) 79.1  (15.88) 81.7  (16.09)
Gemcitabine 79.1  (18.29) 80.8  (12.51) 81.0  (14.49)
8.Secondary Outcome
Title Duration of Exposure
Hide Description Duration of exposure (days) = First dose date of study drug from the last cycle - first dose date of study drug + 21.
Time Frame During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 30 33 35
Median (Full Range)
Unit of Measure: days
101
(21 to 469)
161
(42 to 637)
168
(21 to 436)
9.Secondary Outcome
Title Number of Cycles Participants Received Treatment in Each Treatment Arm
Hide Description Participants were considered to have started a cycle if they have received at least 1 dose of any study drug.
Time Frame During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days
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Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 30 33 35
Mean (Standard Deviation)
Unit of Measure: number of cycles
6  (5.0) 9  (6.6) 8  (4.8)
10.Secondary Outcome
Title Cumulative Dose of Gemcitabine
Hide Description Cumulative dose: Sum of the total doses by cycle administered to a participant in the duration of exposure, i.e. total number of cycles received (milligram per meter square [mg/m^2]).
Time Frame During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days
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Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 30 33 35
Mean (Standard Deviation)
Unit of Measure: mg/m^2
10694.3  (9029.11) 14680.9  (11557.90) 13277.2  (8722.51)
11.Secondary Outcome
Title Cumulative Dose of Carboplatin
Hide Description Cumulative dose: Sum of the total doses by cycle (AUC) administered to a participant in the duration of exposure, i.e. total number of cycles received (in total prescribed AUC).
Time Frame During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days
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Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 30 33 35
Mean (Standard Deviation)
Unit of Measure: AUC (mg/mL/min)
20.3  (16.47) 27.8  (21.21) 26.0  (16.33)
12.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Trilaciclib
Hide Description The observed peak plasma concentration was determined from the plasma concentration-versus time data.
Time Frame Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)
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Hide Analysis Population Description
The pharmacokinetic (PK) analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. Since, no participant received Trilaciclib in Group 1, data was not assessed and reported.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Day 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 0 6 7
Mean (Standard Deviation)
Unit of Measure: ng/mL
2280  (1790) 1630  (423)
13.Secondary Outcome
Title Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Trilaciclib
Hide Description AUC0-t was calculated with the linear/log-trapezoidal method, which uses linear interpolation between data points to calculate the AUC. The linear/log-trapezoidal method will be employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method will be used for those arising from decreasing concentrations.
Time Frame Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)
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Hide Analysis Population Description
The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. Since, no participant received Trilaciclib in Group 1, data was not assessed and reported.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Day 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 0 6 7
Mean (Standard Deviation)
Unit of Measure: hour* nanogram per milliliter (h*ng/mL)
3610  (1870) 3800  (910)
14.Secondary Outcome
Title Terminal Elimination Half-Life (t1/2) of Trilaciclib
Hide Description t1/2 was calculated as 0.693 divided by lambda z. lambda z (terminal phase rate constant) was determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve, the actual body exposure to drug after administration of a dose of the drug ( in mg*h/L).
Time Frame Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. Since, no participant received Trilaciclib in Group 1, data was not assessed and reported.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Day 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 0 5 6
Median (Full Range)
Unit of Measure: hours
5.27
(3.98 to 6.64)
5.31
(4.36 to 6.29)
15.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Gemcitabine
Hide Description The observed peak plasma concentration was determined from the plasma concentration-versus time data.
Time Frame Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)
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Hide Analysis Population Description
The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Day 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 1 5 5
Mean (Standard Deviation)
Unit of Measure: microgram per milliliter (mcg/mL)
NA [1]   (NA) 18.0  (4.04) 23.8  (25.9)
[1]
Data was not available since only one participant had sample in Group 1 and it was sufficient only for assessment of carboplatin.
16.Secondary Outcome
Title Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Gemcitabine
Hide Description AUC0-t was calculated with the linear/log-trapezoidal method.
Time Frame Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)
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Hide Analysis Population Description
The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Day 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 1 5 5
Mean (Standard Deviation)
Unit of Measure: hour*microgram per milliliter (h*mcg/mL)
NA [1]  20.4  (11.6) 15.4  (7.11)
[1]
Data was not available since only one participant had sample in Group 1 and it was sufficient only for assessment of carboplatin.
17.Secondary Outcome
Title Terminal Elimination Half-Life (t1/2) of Free Carboplatin
Hide Description t1/2 was calculated as 0.693 divided by lambda z. lambda z (terminal phase rate constant) was determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve.
Time Frame Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)
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Hide Analysis Population Description
The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received Intravenous (IV) infusion of standard GC chemotherapy (gemcitabine 1000 milligrams per meter square [mg/m^2] and carboplatin area under the curve [AUC] 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 1 5 5
Median (Full Range)
Unit of Measure: hours
5.23
2.49
(1.32 to 2.93)
1.79
(1.35 to 4.86)
18.Secondary Outcome
Title Clearance (CL) of of Free Carboplatin
Hide Description Clearance after intravenous infusion administration was calculated as: CL=Dose/AUC0-inf. AUC0-inf was calculated as: AUC0-inf=AUClast+Clast/lambdaz where Clast is the last quantifiable concentration in the terminal elimination phase.
Time Frame Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received Intravenous (IV) infusion of standard GC chemotherapy (gemcitabine 1000 milligrams per meter square [mg/m^2] and carboplatin area under the curve [AUC] 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 1 3 5
Mean (Standard Deviation)
Unit of Measure: Liter/hour (L/h)
6.65 14.0  (2.80) 13.7  (4.48)
19.Secondary Outcome
Title Volume of Distribution at Steady State (Vss) of Free Carboplatin
Hide Description Vss was the volume of distribution at steady state of free carboplatin was reported.
Time Frame Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)
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Hide Analysis Population Description
The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received Intravenous (IV) infusion of standard GC chemotherapy (gemcitabine 1000 milligrams per meter square [mg/m^2] and carboplatin area under the curve [AUC] 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 1 5 5
Mean (Standard Deviation)
Unit of Measure: Liter
44.4 35.0  (12.0) 34.0  (8.99)
20.Secondary Outcome
Title Number of Participants With Grade 3 and 4 Hematologic Toxicities
Hide Description Hematologic toxicities events were defined as any cycle where any hematologic lab value occurs that meets the CTCAE toxicity grade criteria for >= Grade 3 and the value is treatment emergent. The occurrence of Grade 3 and 4 hematologic toxicities was a binary endpoint. If a participant had at least 1 cycle with at least one Grade 3 or 4 hematologic toxicities during the treatment period, the participant was assigned as Yes to the occurrence of Grade 3 and 4 hematologic toxicities; otherwise, it was No. If a participant did not have an event, the value of 0 was assigned to that participant.
Time Frame During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days
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Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with Grade 3 and 4 hematologic toxicities: Yes
25
  73.5%
30
  90.9%
27
  77.1%
Participants with Grade 3 and 4 hematologic toxicities: No
9
  26.5%
3
   9.1%
8
  22.9%
21.Secondary Outcome
Title Number of Participants With Grade 3 or 4 Thrombocytopenia
Hide Description Hematologic toxicities events are defined as any cycle where any hematologic lab value occurs that meets the CTCAE toxicity grade criteria for >= Grade 3 and the value is treatment emergent. The occurrence of Grade 3 and 4 thrombocytopenia was a binary endpoint. If a participant had at least 1 cycle with at least one Grade 3 or 4 thrombocytopenia during the treatment period, the participant was assigned as "Yes" to the occurrence of Grade 3 and 4 thrombocytopenia; otherwise, it was "No". If a participant did not have an event, the value of 0 was assigned to that participant.
Time Frame During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
21
  61.8%
12
  36.4%
19
  54.3%
22.Secondary Outcome
Title Major Adverse Hematologic Event (MAHE) Rate
Hide Description MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelosuppression into a single endpoint by summing of the total number of events across a set of pre-specified components.The individual components for MAHE were all-cause hospitalizations, all-cause dose reductions, febrile neutropenia, prolonged severe neutropenia (duration > 5 days), RBC transfusion and platelet transfusion. Event rate for MAHE was calculated as the number of events/durations of treatment period divided by 7 days/1 week.
Time Frame During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Measure Type: Number
Unit of Measure: event rate per week
0.153 0.108 0.080
23.Secondary Outcome
Title Number of Participants With Febrile Neutropenia (FN)
Hide Description The criterion for identifying FN was if the PT was "FEBRILE NEUTROPENIA" the occurrence during the treatment period was defined as a binary variable (Yes or No); Yes if total number of events >=1 was observed, No for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant.
Time Frame During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
1
   2.9%
1
   3.0%
0
   0.0%
24.Secondary Outcome
Title Number of Participants With Infection SAEs
Hide Description Number of participants with infection SAEs during the treatment period was defined as a binary variable (Yes or No); Yes if total number of events >=1 was observed, No for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant. The criterion for identifying the proper infection SAE records was as follows: If the system organ class (SOC) from Medical Dictionary for Regulatory Activities (MedDRA) takes value "INFECTIONS AND INFESTATIONS," and the AE was a serious event.
Time Frame During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with Infection SAEs: Yes
2
   5.9%
0
   0.0%
0
   0.0%
Participants with Infection SAEs: No
32
  94.1%
33
 100.0%
35
 100.0%
25.Secondary Outcome
Title Number of Participants With Red Blood Cell (RBC) Transfusions On/After Week 5 (Day 35)
Hide Description Each RBC transfusion with a unique start date on/after 5 weeks on study during the treatment period was defined as a separate event. Occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if the total number of events >=1 was observed and "No" for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.
Time Frame From Day 35 through the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 508 days
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with RBC transfusions on/after Week 5: Yes
12
  35.3%
11
  33.3%
8
  22.9%
Participants with RBC transfusions on/after Week 5: No
22
  64.7%
22
  66.7%
27
  77.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Comments RBC Transfusions in Group 3 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7048
Comments A 1-sided p-value was calculated using Hochberg-based gatekeeping procedure to control the global familywise error rate across the multiple null hypotheses.
Method modified Poisson regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted HR
Estimated Value 0.493
Confidence Interval (2-Sided) 95%
0.226 to 1.073
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1957
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
Comments RBC Transfusions in Group 2 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7272
Comments P-value was calculated using modified Poisson method adjusting for duration of treatment in days accounting for number of prior lines of therapy (0 versus 1 - 2); liver involvement as the stratification factors and baseline hemoglobin as a covariate.
Method Modified Poisson Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted rate ratio
Estimated Value 0.885
Confidence Interval (2-Sided) 95%
0.447 to 1.754
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.3089
Estimation Comments [Not Specified]
26.Secondary Outcome
Title Number of Participants With Platelet Transfusions
Hide Description Each platelet transfusion with a unique start date during the treatment period was defined as a separate event. The occurrence during the treatment period was defined as a binary variable (Yes or No); Yes if the total number of events >=1 was observed and No for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.
Time Frame During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with platelet transfusion: Yes
4
  11.8%
3
   9.1%
6
  17.1%
Participants with platelet transfusion: No
30
  88.2%
30
  90.9%
29
  82.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Comments Platelet Transfusions in Group 3 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7048
Comments A 1-sided p-value was calculated using Hochberg-based gatekeeping procedure to control the global familywise error rate across the multiple null hypotheses.
Method modified Poisson regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted rate ratio
Estimated Value 0.988
Confidence Interval (2-Sided) 95%
0.294 to 3.317
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.6105
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
Comments Platelet Transfusions in Group 2 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4078
Comments P-value: calculated using modified Poisson method adjusting for duration of treatment in days accounting for number of prior lines of therapy (0 versus 1 - 2); liver involvement as stratification factors and baseline platelet count as a covariate.
Method Modified Poisson Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted rate ratio
Estimated Value 0.527
Confidence Interval (2-Sided) 95%
0.116 to 2.399
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.4077
Estimation Comments [Not Specified]
27.Secondary Outcome
Title Number of Participants With Granulocyte Colony-stimulating Factor (G-CSF) Administration
Hide Description The criterion for selecting proper records is as follows: If the chemical subgroup from the World Health Organization-Drug Dictionary (WHO-DD) takes value "COLONY STIMULATING FACTOR," the medication was classified as G-CSF. The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if the total number of events >=1 was observed and "No" for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.
Time Frame During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with G-CSF Administration: Yes
16
  47.1%
21
  63.6%
14
  40.0%
Participants with G-CSF Administration: No
18
  52.9%
12
  36.4%
21
  60.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Comments G-CSF Administration in Group 3 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7048
Comments A 1-sided p-value was calculated using Hochberg-based gatekeeping procedure to control the global familywise error rate across the multiple null hypotheses.
Method modified Poisson regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted rate ratio
Estimated Value 0.645
Confidence Interval (2-Sided) 95%
0.362 to 1.150
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1902
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
Comments G-CSF Administration in Group 2 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7835
Comments P-value was calculated using modified Poisson method adjusting for number of cycles, accounting for the number of prior lines of therapy (0 versus 1 - 2) and liver involvement as the stratification factors and baseline ANC as a covariate.
Method Modified Poisson Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted rate ratio
Estimated Value 0.936
Confidence Interval (2-Sided) 95%
0.583 to 1.502
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2260
Estimation Comments [Not Specified]
28.Secondary Outcome
Title Number of Participants With Erythropoiesis Stimulating Agent (ESA) Administration
Hide Description The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if total number of events >=1 was observed, "No" for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant. The criterion to select proper records was as follows: If the chemical subgroup from WHO-DD Version September 2017 (i.e., TEXT4 for CODE4) takes value "OTHER ANTIANEMIC PREPARATIONS", the medication was classified as ESAs.
Time Frame During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with ESA Administration: Yes
4
  11.8%
2
   6.1%
3
   8.6%
Participants with ESA Administration: No
30
  88.2%
31
  93.9%
32
  91.4%
29.Secondary Outcome
Title Number of Participants With Intravenous Antibiotics Use
Hide Description The criteria for identifying an IV antibiotic administration event was (1) if the Therapeutic subgroup from WHO-DD version takes value "ANTIBACTERIALS FOR SYSTEMIC USE", and (2) the route of medication was "intravenous" or the route was "other" with the detailed specification as "IVPB". The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if total number of events >=1 was observed, "No" for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant.
Time Frame During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Day 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with Intravenous Antibiotics Use: Yes
6
  17.6%
5
  15.2%
0
   0.0%
Participants with Intravenous Antibiotics Use: No
28
  82.4%
28
  84.8%
35
 100.0%
30.Secondary Outcome
Title All-cause Dose Reductions, Event Rate (Per Cycle)
Hide Description Dose reductions were not permitted for trilaciclib. Dose reductions for gemcitabine or carboplatin were collected on the dosing page. No more than 3 dose modifications for toxicity in total were allowed for any participant. All dose reductions were counted as a separate event. Discontinuations of an individual component of the chemotherapy regimen were counted as a dose reduction If the participant continued the other chemotherapy drug as a monotherapy. Event rate was calculated as the total number of cycles with an event divided by the total number of cycles.
Time Frame During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 34 33 35
Measure Type: Number
Unit of Measure: event rate per cycle
0.141 0.118 0.133
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Comments All-cause Dose Reductions in Group 3 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7048
Comments The 1-sided p-value was calculated using Hochberg-based gatekeeping procedure to control the global family wise error rate across the multiple null hypotheses.
Method negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted rate ratio
Estimated Value 0.991
Confidence Interval (2-Sided) 95%
0.475 to 2.067
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.3718
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
Comments All-cause Dose Reductions in Group 2 vs Group 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5541
Comments P-value was calculated using negative binomial method adjusting for number of cycles, accounting for the number of prior lines of therapy (0 versus 1 - 2) and liver involvement as the stratification factors.
Method negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted rate ratio
Estimated Value 0.820
Confidence Interval (2-Sided) 95%
0.426 to 1.580
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2744
Estimation Comments [Not Specified]
31.Secondary Outcome
Title Dose Modifications: Number of Participants With Cycle Delays
Hide Description Dose modifications was summarized for each study drug based on number of cycles received during the treatment period. If the participant was unable to start a new cycle at that next visit, then the cycle is delayed, the reason entered, and the question was asked again at the next visit until the participant either starts a new cycle or discontinues treatment.
Time Frame During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 30 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
17
  56.7%
19
  57.6%
22
  62.9%
32.Secondary Outcome
Title Dose Modifications - Number of Participants With Skipped Doses
Hide Description Dose modifications was summarized for each study drug based on skipped doses not received during the treatment period. Primary reasons for skipped doses included toxicity, investigator decision and administrative reasons (e.g., holidays).
Time Frame During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 30 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
15
  50.0%
20
  60.6%
13
  37.1%
33.Secondary Outcome
Title Dose Modifications: Number of Participants With Any Dose Interruptions
Hide Description Dose interruptions was defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.
Time Frame During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 30 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
Trilaciclib NA [1] 
3
   9.1%
5
  14.3%
Carboplatin
1
   3.3%
1
   3.0%
0
   0.0%
Gemcitabine
2
   6.7%
4
  12.1%
0
   0.0%
[1]
Here, 'NA' signifies that Trilaciclib drug was not administered in this specified arm.
34.Secondary Outcome
Title Dose Modifications - Number of Participants With Dose Reductions
Hide Description Dose (mg/m2) reductions were not permitted for trilaciclib. Dose reductions for carboplatin and gemcitabine were determined by comparing the planned dose on the respective drug administration pages between the current cycle and the previous cycle.
Time Frame During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days
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Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 30 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
Carboplatin
10
  33.3%
13
  39.4%
15
  42.9%
Gemcitabine
13
  43.3%
20
  60.6%
17
  48.6%
35.Other Pre-specified Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Hide Description An Adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product that did not necessarily have a causal relationship with this treatment. Any AE that started on or after the first dose of study drugs was included as a TEAE. A Serious AE was defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) and regardless of causality that met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. TEAEs included serious and non-serious TEAEs.
Time Frame During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 1116 days
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Hide Analysis Population Description
The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description:
Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Overall Number of Participants Analyzed 30 33 35
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with any TEAEs
30
 100.0%
33
 100.0%
34
  97.1%
Participants with any Serious TEAEs
10
  33.3%
11
  33.3%
4
  11.4%
Time Frame From date of randomization up to 1121 days
Adverse Event Reporting Description Safety evaluations were conducted at baseline and throughout the study. Safety surveillance reporting of AEs and SAEs commenced at the time of informed consent and continued through 30 days after the last dose of study drug (safety follow-up phone call). The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
 
Arm/Group Title Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib (G1T28)+ Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Hide Arm/Group Description Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg). Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy. Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
All-Cause Mortality
Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib (G1T28)+ Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   25/30 (83.33%)      13/33 (39.39%)      20/35 (57.14%)    
Hide Serious Adverse Events
Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib (G1T28)+ Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/30 (33.33%)      11/33 (33.33%)      4/35 (11.43%)    
Blood and lymphatic system disorders       
Febrile neutropenia * 1  1/30 (3.33%)  1 1/33 (3.03%)  1 0/35 (0.00%)  0
Normochromic normocytic anaemia * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 0/35 (0.00%)  0
Thrombocytopenia * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 0/35 (0.00%)  0
Cardiac disorders       
Acute left ventricular failure * 1  0/30 (0.00%)  0 0/33 (0.00%)  0 1/35 (2.86%)  1
Acute myocardial infarction * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 0/35 (0.00%)  0
Cardiac arrest * 1  0/30 (0.00%)  0 0/33 (0.00%)  0 1/35 (2.86%)  1
Pericardial effusion * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 0/35 (0.00%)  0
Right ventricular failure * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 0/35 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain * 1  0/30 (0.00%)  0 0/33 (0.00%)  0 1/35 (2.86%)  1
Ascites * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 0/35 (0.00%)  0
Enteritis * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 0/35 (0.00%)  0
Faecaloma * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 0/35 (0.00%)  0
Oesophageal stenosis * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 0/35 (0.00%)  0
Varices oesophageal * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 0/35 (0.00%)  0
General disorders       
Non-cardiac chest pain * 1  0/30 (0.00%)  0 0/33 (0.00%)  0 1/35 (2.86%)  2
Pain * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 0/35 (0.00%)  0
Infections and infestations       
Cellulitis * 1  2/30 (6.67%)  2 0/33 (0.00%)  0 0/35 (0.00%)  0
Bacteraemia * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 0/35 (0.00%)  0
Lung infection * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 0/35 (0.00%)  0
Septic shock * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 0/35 (0.00%)  0
Injury, poisoning and procedural complications       
Lumbar vertebral fracture * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 0/35 (0.00%)  0
Subdural haematoma * 1  0/30 (0.00%)  0 0/33 (0.00%)  0 1/35 (2.86%)  1
Investigations       
Platelet count decreased * 1  0/30 (0.00%)  0 2/33 (6.06%)  2 0/35 (0.00%)  0
Metabolism and nutrition disorders       
Diabetic ketoacidosis * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 0/35 (0.00%)  0
Hypercalcaemia * 1  0/30 (0.00%)  0 0/33 (0.00%)  0 1/35 (2.86%)  1
Musculoskeletal and connective tissue disorders       
Myositis * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 0/35 (0.00%)  0
Nervous system disorders       
Syncope * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 0/35 (0.00%)  0
Psychiatric disorders       
Suicidal ideation * 1  0/30 (0.00%)  0 0/33 (0.00%)  0 1/35 (2.86%)  1
Renal and urinary disorders       
Haematuria * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 0/35 (0.00%)  0
Urinary tract obstruction * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 0/35 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Dyspnoea * 1  1/30 (3.33%)  2 1/33 (3.03%)  1 0/35 (0.00%)  0
Pleural effusion * 1  0/30 (0.00%)  0 2/33 (6.06%)  2 0/35 (0.00%)  0
Pulmonary embolism * 1  0/30 (0.00%)  0 2/33 (6.06%)  2 0/35 (0.00%)  0
Acute respiratory failure * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 0/35 (0.00%)  0
Obstructive airways disorder * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 0/35 (0.00%)  0
Pleuritic pain * 1  0/30 (0.00%)  0 0/33 (0.00%)  0 1/35 (2.86%)  1
Vascular disorders       
Embolism * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 0/35 (0.00%)  0
Hypertension * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 0/35 (0.00%)  0
Hypotension * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 0/35 (0.00%)  0
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Group 2: Trilaciclib (G1T28)+ Gemcitabine/Carboplatin (Days 1 and 8) Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   30/30 (100.00%)      33/33 (100.00%)      34/35 (97.14%)    
Blood and lymphatic system disorders       
Anaemia * 1  22/30 (73.33%)  61 16/33 (48.48%)  46 15/35 (42.86%)  35
Neutropenia * 1  13/30 (43.33%)  49 15/33 (45.45%)  79 12/35 (34.29%)  31
Thrombocytopenia * 1  13/30 (43.33%)  68 13/33 (39.39%)  55 11/35 (31.43%)  55
Leukopenia * 1  5/30 (16.67%)  9 3/33 (9.09%)  12 1/35 (2.86%)  3
Ear and labyrinth disorders       
Tinnitus * 1  0/30 (0.00%)  0 2/33 (6.06%)  2 0/35 (0.00%)  0
Eye disorders       
Lacrimation increased * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 2/35 (5.71%)  2
Gastrointestinal disorders       
Nausea * 1  7/30 (23.33%)  8 14/33 (42.42%)  19 17/35 (48.57%)  31
Vomiting * 1  8/30 (26.67%)  9 8/33 (24.24%)  23 11/35 (31.43%)  18
Constipation * 1  5/30 (16.67%)  6 9/33 (27.27%)  16 9/35 (25.71%)  11
Diarrhoea * 1  4/30 (13.33%)  4 9/33 (27.27%)  15 5/35 (14.29%)  6
Gastrooesophageal reflux disease * 1  3/30 (10.00%)  3 5/33 (15.15%)  5 1/35 (2.86%)  1
Abdominal pain * 1  1/30 (3.33%)  1 4/33 (12.12%)  6 2/35 (5.71%)  3
Abdominal pain upper * 1  1/30 (3.33%)  1 3/33 (9.09%)  3 3/35 (8.57%)  3
Stomatitis * 1  2/30 (6.67%)  5 1/33 (3.03%)  1 2/35 (5.71%)  3
Abdominal distension * 1  0/30 (0.00%)  0 3/33 (9.09%)  3 1/35 (2.86%)  1
Flatulence * 1  0/30 (0.00%)  0 2/33 (6.06%)  2 0/35 (0.00%)  0
General disorders       
Fatigue * 1  11/30 (36.67%)  17 14/33 (42.42%)  22 16/35 (45.71%)  35
Oedema peripheral * 1  4/30 (13.33%)  5 4/33 (12.12%)  7 4/35 (11.43%)  8
Pyrexia * 1  3/30 (10.00%)  3 6/33 (18.18%)  8 2/35 (5.71%)  2
Pain * 1  5/30 (16.67%)  7 2/33 (6.06%)  2 3/35 (8.57%)  3
Chills * 1  0/30 (0.00%)  0 6/33 (18.18%)  7 1/35 (2.86%)  1
Influenza like illness * 1  0/30 (0.00%)  0 0/33 (0.00%)  0 4/35 (11.43%)  5
Catheter site pain * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 2/35 (5.71%)  2
Chest pain * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 2/35 (5.71%)  2
Chest discomfort * 1  0/30 (0.00%)  0 0/33 (0.00%)  0 2/35 (5.71%)  4
Infusion site pain * 1  0/30 (0.00%)  0 0/33 (0.00%)  0 2/35 (5.71%)  2
Mucosal inflammation * 1  0/30 (0.00%)  0 2/33 (6.06%)  2 0/35 (0.00%)  0
Infections and infestations       
Urinary tract infection * 1  5/30 (16.67%)  5 4/33 (12.12%)  4 3/35 (8.57%)  4
Pneumonia * 1  1/30 (3.33%)  1 3/33 (9.09%)  3 0/35 (0.00%)  0
Sinusitis * 1  1/30 (3.33%)  1 1/33 (3.03%)  1 2/35 (5.71%)  3
Upper respiratory tract infection * 1  1/30 (3.33%)  1 2/33 (6.06%)  3 0/35 (0.00%)  0
Nasopharyngitis * 1  2/30 (6.67%)  2 0/33 (0.00%)  0 0/35 (0.00%)  0
Injury, poisoning and procedural complications       
Infusion related reaction * 1  1/30 (3.33%)  1 7/33 (21.21%)  35 4/35 (11.43%)  6
Investigations       
Neutrophil count decreased * 1  8/30 (26.67%)  20 12/33 (36.36%)  50 11/35 (31.43%)  30
Platelet count decreased * 1  8/30 (26.67%)  38 8/33 (24.24%)  13 12/35 (34.29%)  44
Alanine aminotransferase increased * 1  3/30 (10.00%)  5 4/33 (12.12%)  6 4/35 (11.43%)  4
Aspartate aminotransferase increased * 1  3/30 (10.00%)  6 4/33 (12.12%)  5 4/35 (11.43%)  7
White blood cell count decreased * 1  2/30 (6.67%)  7 4/33 (12.12%)  7 2/35 (5.71%)  5
Blood alkaline phosphatase increased * 1  2/30 (6.67%)  2 2/33 (6.06%)  2 0/35 (0.00%)  0
Weight decreased * 1  0/30 (0.00%)  0 2/33 (6.06%)  3 1/35 (2.86%)  1
Haemoglobin decreased * 1  0/30 (0.00%)  0 2/33 (6.06%)  2 0/35 (0.00%)  0
Weight increased * 1  0/30 (0.00%)  0 0/33 (0.00%)  0 2/35 (5.71%)  2
Metabolism and nutrition disorders       
Hypokalaemia * 1  3/30 (10.00%)  3 4/33 (12.12%)  5 5/35 (14.29%)  5
Decreased appetite * 1  2/30 (6.67%)  2 5/33 (15.15%)  6 4/35 (11.43%)  7
Hypomagnesaemia * 1  2/30 (6.67%)  2 1/33 (3.03%)  1 2/35 (5.71%)  2
Hyponatraemia * 1  1/30 (3.33%)  3 2/33 (6.06%)  2 2/35 (5.71%)  2
Musculoskeletal and connective tissue disorders       
Back pain * 1  3/30 (10.00%)  3 7/33 (21.21%)  15 3/35 (8.57%)  5
Arthralgia * 1  3/30 (10.00%)  4 6/33 (18.18%)  7 3/35 (8.57%)  4
Pain in extremity * 1  2/30 (6.67%)  3 4/33 (12.12%)  6 3/35 (8.57%)  4
Bone pain * 1  4/30 (13.33%)  5 2/33 (6.06%)  2 2/35 (5.71%)  3
Myalgia * 1  5/30 (16.67%)  5 2/33 (6.06%)  2 1/35 (2.86%)  1
Musculoskeletal chest pain * 1  1/30 (3.33%)  1 2/33 (6.06%)  3 3/35 (8.57%)  3
Musculoskeletal pain * 1  1/30 (3.33%)  1 1/33 (3.03%)  1 4/35 (11.43%)  6
Flank pain * 1  0/30 (0.00%)  0 3/33 (9.09%)  6 1/35 (2.86%)  2
Muscular weakness * 1  0/30 (0.00%)  0 3/33 (9.09%)  3 0/35 (0.00%)  0
Hypophosphataemia * 1  0/30 (0.00%)  0 3/33 (9.09%)  4 3/35 (8.57%)  7
Dehydration * 1  4/30 (13.33%)  4 0/33 (0.00%)  0 1/35 (2.86%)  1
Hypoalbuminaemia * 1  1/30 (3.33%)  1 1/33 (3.03%)  2 2/35 (5.71%)  2
Hypocalcaemia * 1  1/30 (3.33%)  3 2/33 (6.06%)  2 0/35 (0.00%)  0
Hyperlipidaemia * 1  2/30 (6.67%)  2 0/33 (0.00%)  0 0/35 (0.00%)  0
Nervous system disorders       
Headache * 1  6/30 (20.00%)  9 9/33 (27.27%)  11 14/35 (40.00%)  22
Dizziness * 1  6/30 (20.00%)  8 4/33 (12.12%)  7 6/35 (17.14%)  11
Dysgeusia * 1  0/30 (0.00%)  0 5/33 (15.15%)  5 1/35 (2.86%)  1
Cognitive disorders * 1  1/30 (3.33%)  1 2/33 (6.06%)  2 1/35 (2.86%)  1
Restless legs syndrome * 1  0/30 (0.00%)  0 2/33 (6.06%)  2 1/35 (2.86%)  1
Burning sensation * 1  0/30 (0.00%)  0 0/33 (0.00%)  0 2/35 (5.71%)  2
Psychiatric disorders       
Anxiety * 1  3/30 (10.00%)  3 2/33 (6.06%)  2 4/35 (11.43%)  4
Depression * 1  3/30 (10.00%)  3 5/33 (15.15%)  5 1/35 (2.86%)  1
Insomnia * 1  4/30 (13.33%)  4 1/33 (3.03%)  1 4/35 (11.43%)  4
Renal and urinary disorders       
Pollakiuria * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 2/35 (5.71%)  2
Acute kidney injury * 1  0/30 (0.00%)  0 2/33 (6.06%)  4 0/35 (0.00%)  0
Reproductive system and breast disorders       
Breast pain * 1  3/30 (10.00%)  3 1/33 (3.03%)  4 3/35 (8.57%)  3
Respiratory, thoracic and mediastinal disorders       
Dyspnoea * 1  3/30 (10.00%)  3 9/33 (27.27%)  10 6/35 (17.14%)  7
Cough * 1  2/30 (6.67%)  2 8/33 (24.24%)  8 7/35 (20.00%)  9
Nasal congestion * 1  1/30 (3.33%)  1 2/33 (6.06%)  4 4/35 (11.43%)  4
Oropharyngeal pain * 1  1/30 (3.33%)  1 1/33 (3.03%)  1 2/35 (5.71%)  2
Pleural effusion * 1  0/30 (0.00%)  0 3/33 (9.09%)  4 0/35 (0.00%)  0
Upper-airway cough syndrome * 1  1/30 (3.33%)  1 2/33 (6.06%)  2 1/35 (2.86%)  1
Skin and subcutaneous tissue disorders       
Alopecia * 1  1/30 (3.33%)  1 5/33 (15.15%)  5 6/35 (17.14%)  6
Pruritus * 1  1/30 (3.33%)  1 3/33 (9.09%)  3 4/35 (11.43%)  5
Erythema * 1  0/30 (0.00%)  0 4/33 (12.12%)  21 3/35 (8.57%)  4
Rash * 1  1/30 (3.33%)  1 3/33 (9.09%)  3 3/35 (8.57%)  4
Rash maculo-papular * 1  1/30 (3.33%)  4 2/33 (6.06%)  4 1/35 (2.86%)  1
Vascular disorders       
Hypertension * 1  2/30 (6.67%)  2 2/33 (6.06%)  2 1/35 (2.86%)  7
Hot flush * 1  2/30 (6.67%)  2 2/33 (6.06%)  2 0/35 (0.00%)  0
Thrombophlebitis superficial * 1  0/30 (0.00%)  0 1/33 (3.03%)  1 3/35 (8.57%)  7
Hypotension * 1  1/30 (3.33%)  1 0/33 (0.00%)  0 2/35 (5.71%)  2
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
Limitations of this study are the small sample size and open-label design. Antitumor outcomes were not the primary endpoints.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The investigator will submit results communications for review by the sponsor at least 60 days prior to expected submission to the intended publisher or meeting committee. This review period may be shortened upon mutual consent. The sponsor may request modification of any publication, presentation or use by the investigator if such activity may jeopardize a patent application, an existing patent, or other proprietary rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Info
Organization: G1 Therapeutics, Inc
Phone: +1 9192139835
EMail: clinicalinfo@g1therapeutics.com
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Responsible Party: G1 Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02978716    
Other Study ID Numbers: G1T28-04
2016-004466-26 ( EudraCT Number )
First Submitted: November 18, 2016
First Posted: December 1, 2016
Results First Submitted: January 6, 2022
Results First Posted: March 23, 2022
Last Update Posted: March 23, 2022