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

• ClinicalTrials.gov Identifier: NCT02978716
• Recruitment Status: Terminated
• First Posted: December 1, 2016
• Results First Posted: March 23, 2022
• Last Update Posted: March 23, 2022
• Sponsor: G1 Therapeutics, Inc.
• Information provided by (Responsible Party): G1 Therapeutics, Inc.

Study Description

Brief Summary:

This was a study to investigate the potential clinical benefit of trilaciclib (G1T28) in preserving the bone marrow and the immune system, and enhancing chemotherapy antitumor efficacy when administered prior to carboplatin and gemcitabine (GC therapy) for participants with metastatic triple negative breast cancer.

The study was an open-label and 102 participants were randomly assigned (1:1:1 fashion) to 1 of the 3 following treatment groups:

• Group 1: GC therapy (Days 1 and 8 of 21-day cycles) only (n=34)
• Group 2: GC therapy (Days 1 and 8) plus trilaciclib (G1T28) on Days 1 and 8 of 21-day cycles (n=33)
• Group 3: GC therapy (Days 2 and 9) plus trilaciclib (G1T28) on Days 1, 2, 8, and 9 of 21-day cycles (n=35)

The study included 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit.

Condition or disease	Intervention/treatment	Phase
Triple-Negative Breast Neoplasms; Breast Neoplasm; Breast Cancer; Triple-Negative Breast Cancer	Drug: Trilaciclib; Drug: Gemcitabine; Drug: Carboplatin	Phase 2

Detailed Description:

The posted results represent the final results of Study G1T28-04, a Phase 2 study of the safety, efficacy and pharmacokinetics of trilaciclib (G1T28) in patients with locally recurrent/metastatic triple negative breast cancer receiving gemcitabine and carboplatin chemotherapy.

The final myelopreservation efficacy results are reported from database lock 1 ([DBL1], data cut-off [DCO] date of 30 July 2018). Final anti-tumor efficacy (ORR, PFS), and final summary exposure and safety data are reported from database lock 2 ([DBL2], DCO 28 June 2019) which occurred to support filing of the trilaciclib New Drug Application (NDA). Final overall survival (OS) data are reported from the final database lock which occurred on 17 July 2020 (with a last patient last visit date of 28 February 2020).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of the Safety, Efficacy, and Pharmacokinetics of G1T28 in Patients With Metastatic Triple Negative Breast Cancer Receiving Gemcitabine and Carboplatin Chemotherapy
• Actual Study Start Date: February 2, 2017
• Actual Primary Completion Date: June 28, 2019
• Actual Study Completion Date: February 28, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1: Gemcitabine/Carboplatin (Days 1 and 8); 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 cycle. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Drug: Gemcitabine; Gemcitabine; Drug: Carboplatin; Carboplatin
Experimental: Group 2: Trilaciclib + Gemcitabine/ Carboplatin (Days 1 and 8); 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 cycle. Trilaciclib was administered prior to chemotherapy.	Drug: Trilaciclib; G1T28; Other Names: G1T28; CDK 4/6 Inhibitor; Drug: Gemcitabine; Gemcitabine; Drug: Carboplatin; Carboplatin
Experimental: Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9); 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 Cycle. Trilaciclib was administered prior to chemotherapy.	Drug: Trilaciclib; G1T28; Other Names: G1T28; CDK 4/6 Inhibitor; Drug: Gemcitabine; Gemcitabine; Drug: Carboplatin; Carboplatin

Outcome Measures

Primary Outcome Measures :

1. Duration of Severe (Grade 4) Neutropenia (DSN) During Cycle 1 [ Time Frame: From randomization to the end of Cycle 1 (Each cycle= 21 days) ]
   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.
2. Number of Participants With Severe (Grade 4) Neutropenia (SN) [ 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 ]
   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".

Secondary Outcome Measures :

1. Number of Participants With Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days ]
   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.
2. Duration of Objective Response (DOR) as Per RECIST v1.1 as Determined by Investigator [ Time Frame: From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days ]
   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.
3. Overall Survival (OS) [ Time Frame: From date of randomization to date of death due to any cause, assessed up to a maximum of 1120 days ]
   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.
4. Progression Free Survival (PFS) as Per RECIST v1.1 as Determined by Investigator [ 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 ]
   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.
5. Relative Dose Intensity of Gemcitabine and Carboplatin [ 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 ]
   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).
6. Duration of Exposure [ 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 ]
   Duration of exposure (days) = First dose date of study drug from the last cycle - first dose date of study drug + 21.
7. Number of Cycles Participants Received Treatment in Each Treatment Arm [ 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 ]
   Participants were considered to have started a cycle if they have received at least 1 dose of any study drug.
8. Cumulative Dose of Gemcitabine [ 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 ]
   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]).
9. Cumulative Dose of Carboplatin [ 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 ]
   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).
10. Maximum Observed Plasma Concentration (Cmax) of Trilaciclib [ 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) ]
    The observed peak plasma concentration was determined from the plasma concentration-versus time data.
11. Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Trilaciclib [ 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) ]
    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.
12. Terminal Elimination Half-Life (t1/2) of Trilaciclib [ 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) ]
    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).
13. Maximum Observed Plasma Concentration (Cmax) of Gemcitabine [ 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) ]
    The observed peak plasma concentration was determined from the plasma concentration-versus time data.
14. Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Gemcitabine [ 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) ]
    AUC0-t was calculated with the linear/log-trapezoidal method.
15. Terminal Elimination Half-Life (t1/2) of Free Carboplatin [ 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) ]
    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.
16. Clearance (CL) of of Free Carboplatin [ 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) ]
    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.
17. Volume of Distribution at Steady State (Vss) of Free Carboplatin [ 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) ]
    Vss was the volume of distribution at steady state of free carboplatin was reported.
18. Number of Participants With Grade 3 and 4 Hematologic Toxicities [ 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 ]
    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.
19. Number of Participants With Grade 3 or 4 Thrombocytopenia [ 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 ]
    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.
20. Major Adverse Hematologic Event (MAHE) Rate [ 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 ]
    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.
21. Number of Participants With Febrile Neutropenia (FN) [ 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 ]
    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.
22. Number of Participants With Infection SAEs [ 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 ]
    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.
23. Number of Participants With Red Blood Cell (RBC) Transfusions On/After Week 5 (Day 35) [ 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 ]
    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.
24. Number of Participants With Platelet Transfusions [ 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 ]
    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.
25. Number of Participants With Granulocyte Colony-stimulating Factor (G-CSF) Administration [ 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 ]
    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.
26. Number of Participants With Erythropoiesis Stimulating Agent (ESA) Administration [ 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 ]
    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.
27. Number of Participants With Intravenous Antibiotics Use [ 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 ]
    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.
28. All-cause Dose Reductions, Event Rate (Per Cycle) [ 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 ]
    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.
29. Dose Modifications: Number of Participants With Cycle Delays [ 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 ]
    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.
30. Dose Modifications - Number of Participants With Skipped Doses [ 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 ]
    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).
31. Dose Modifications: Number of Participants With Any Dose Interruptions [ 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 ]
    Dose interruptions was defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.
32. Dose Modifications - Number of Participants With Dose Reductions [ 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 ]
    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.

Other Outcome Measures:

1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and 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 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Confirmed diagnosis of hormone receptor (HR)-negative, human epidermal growth factor receptor 2 (HER2)-negative (locally recurrent or metastatic TNBC) breast cancer
• Available TNBC diagnostic tumor tissue (archived tissue allowed)
• Evaluable disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Adequate organ function
• Predicted life expectancy of 3 or more months

Exclusion Criteria:

• More than 2 prior chemotherapy regimens for locally recurrent or metastatic TNBC. If > 12 months have elapsed between the date of last adjuvant/neoadjuvant chemotherapy administration and first documented local or distant disease recurrence the therapy will not be considered a line of therapy in the locally recurrent or metastatic TNBC setting.
• CNS metastases or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
• Investigational drug within 30 days of first trilaciclib (G1T28) dose
• Concurrent radiotherapy, radiotherapy within 14 days of first trilaciclib (G1T28) dose
• Cytotoxic chemotherapy within 3 weeks of first trilaciclib (G1T28) dose
• Prior hematopoietic stem cell or bone marrow transplantation

Contacts and Locations

Locations

United States, Arizona

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, United States, 85704

United States, California

Disney Family Cancer Center

Burbank, California, United States, 91505

Sharp Clinical Oncology

San Diego, California, United States, 92123

Innovative Clinical Research Institute

Whittier, California, United States, 90603

United States, Colorado

Memorial UC Health

Colorado Springs, Colorado, United States, 80909

Rocky Mountain Cancer Centers

Lakewood, Colorado, United States, 80228

United States, Florida

Florida Cancer Specialists

Fort Myers, Florida, United States, 33916

Florida Cancer Research Institute, LLC.

Plantation, Florida, United States, 33324

Florida Cancer Specialists - North (FCS North)

Saint Petersburg, Florida, United States, 33705

Moffitt Cancer Center

Tampa, Florida, United States, 33612

Florida Cancer Specialists - East (FCS East)

West Palm Beach, Florida, United States, 33401

United States, Idaho

Saint Alphonsus Regional Medical Center

Boise, Idaho, United States, 83706

United States, Illinois

Illinois Cancer Specialists

Arlington Heights, Illinois, United States, 60005

United States, Indiana

Community Health Network

Indianapolis, Indiana, United States, 46250

United States, Maryland

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States, 21201-1544

The University of Maryland St. Joseph Medical Center

Towson, Maryland, United States, 21204

United States, Missouri

Saint Luke's Cancer Institute

Kansas City, Missouri, United States, 64113

United States, Nevada

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States, 89128

United States, North Carolina

Levine Cancer Center

Charlotte, North Carolina, United States, 28204

Forsyth Memorial Hospital, Novant Health Oncology Specialists

Winston-Salem, North Carolina, United States, 27103

United States, Tennessee

Tennessee Oncology

Chattanooga, Tennessee, United States, 37404

Tennessee Oncology

Nashville, Tennessee, United States, 37203

United States, Texas

Texas Oncology-Dallas Presbyterian Hospital

Austin, Texas, United States, 75231

Texas Oncology, P.A.

Austin, Texas, United States, 78745

Texas Oncology, P.A.

Bedford, Texas, United States, 76022

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States, 75246

Texas Oncology-El Paso Cancer Treatment Center Grandview

El Paso, Texas, United States, 79902

The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States, 76104

Texas Oncology-San Antonio Northeast

San Antonio, Texas, United States, 78217

Tyler Hematology-Oncology, PA

Tyler, Texas, United States, 75701

Texas Oncology, P.A.

Tyler, Texas, United States, 75702

United States, Virginia

University of Virginia

Charlottesville, Virginia, United States, 22908

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States, 22031

Virginia Oncology Associates

Virginia Beach, Virginia, United States, 23456

United States, Washington

Northwest Medical Specialties, PLLC

Tacoma, Washington, United States, 98405

Belgium

Antwerp University Hospital (UZA)

Edegem, Belgium, 10 2650

Bulgaria

University Multiprofile Hospital for Active Treatment

Sofia, Bulgaria, 1000

MHAT for Womens Health - Nadezhda OOD

Sofia, Bulgaria, 1330

Special Hospital For Active Treatment In Oncology

Sofia, Bulgaria, 1756

Multiprofile Hospital for Active Treatment

Varna, Bulgaria, 9000

Croatia

University Hospital Centre Osijek

Osijek, Croatia, 31000

General Hospital Varaždin

Varazdin, Croatia, 42000

University Hospital Centre "Sestre milosrdnice"

Zagreb, Croatia, 10000

University Hospital Centre Zagreb

Zagreb, Croatia, 10000

North Macedonia

Clinical Hospital Dr. Trifun Panovski

Bitola, North Macedonia, 7000

University Clinic of Radiotherapy and Oncology

Skopje, North Macedonia, 1000

Serbia

Special Hospital for Internal Diseases , Oncomed

Belgrade, Serbia, 11000

Clinical Hospital Centre Bezanijska Kosa, Oncology Clinic

Belgrade, Serbia, 11070

Center for Oncology and Radiotherapy, Clinical Centre

Kragujevac, Serbia, 34000

Clinical Centre Nis, Clinic of Oncology

Nis, Serbia, 18000

Oncology Institute of Vojvodina, Clinic for Internal Oncology

Sremska Kamenica, Serbia, 21204

Slovakia

Mammacentrum, Sv.Agáty

Banská Bystrica, Slovakia, 974 01

Cancer Institute VOU, Rastislavova

Košice, Slovakia, 040 01

Slovenia

University Medical Centre Maribor

Maribor, Slovenia, 2000

Sponsors and Collaborators

G1 Therapeutics, Inc.

Investigators

• Study Director: Clinical Contact; G1 Therapeutics, Inc.

  Study Documents (Full-Text)

Documents provided by G1 Therapeutics, Inc.:

Study Protocol  [PDF] August 31, 2017

Statistical Analysis Plan  [PDF] September 28, 2018

More Information

Publications:

Tan AR, Wright GS, Thummala AR, Danso MA, Popovic L, Pluard TJ, Han HS, Vojnović Ž, Vasev N, Ma L, Richards DA, Wilks ST, Milenković D, Yang Z, Antal JM, Morris SR, O'Shaughnessy J. Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol. 2019 Nov;20(11):1587-1601. doi: 10.1016/S1470-2045(19)30616-3. Epub 2019 Sep 28.

Tan AR, Wright GS, Thummala AR, Danso MA, Popovic L, Pluard TJ, Han HS, Vojnović Ž, Vasev N, Ma L, Richards DA, Wilks ST, Milenković D, Xiao J, Sorrentino J, Horton J, O'Shaughnessy J. Trilaciclib Prior to Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer: Final Efficacy and Subgroup Analysis from a Randomized Phase II Study. Clin Cancer Res. 2022 Feb 15;28(4):629-636. doi: 10.1158/1078-0432.CCR-21-2272.

• Responsible Party: G1 Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02978716
• Other Study ID Numbers: G1T28-04; 2016-004466-26 ( EudraCT Number )
• First Posted: December 1, 2016
• Results First Posted: March 23, 2022
• Last Update Posted: March 23, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by G1 Therapeutics, Inc.:

Breast Cancer; CDK 4/6 Inhibitor; Triple Negative Breast Cancer; Metastatic

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms; Triple Negative Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Gemcitabine; Carboplatin; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs