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Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Combination With Pembrolizumab in Participants With Metastatic Triple-Negative Breast Cancer (mTNBC) (ENHANCE-1)

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ClinicalTrials.gov Identifier: NCT02513472
Recruitment Status : Active, not recruiting
First Posted : July 31, 2015
Results First Posted : August 14, 2020
Last Update Posted : August 14, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Eisai Inc.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Neoplasm
Interventions Drug: Eribulin Mesylate
Drug: Pembrolizumab
Enrollment 258
Recruitment Details Participants took part in the study at 18 investigative sites in the United States. Results are reported in this result summary at primary completion date (31 July 2019). A total 258 participants were screened and enrolled, of which 91 were screen failures and 167 were treated. RP2D is recommended Phase 2 dose.
Pre-assignment Details As planned, data is reported based on Stratum 1 (No prior treatment with systemic anticancer therapy) and 2 (prior 1 to 2 lines of systemic anticancer therapy) due to better estimating efficacy data for Stratum 2. All participants enrolled in Phase 1b and treated on RP2D level were pooled with the participants in Phase 2 for efficacy analysis.
Arm/Group Title Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab
Hide Arm/Group Description Participants with metastatic triple negative breast cancer (mTNBC) who were never treated with systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 milligram per square meter (mg/m^2), intravenous infusion on Days 1 and 8 and pembrolizumab 200 milligram (mg), intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1. Participants with mTNBC previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 2.
Period Title: Overall Study
Started 66 101
Phase 1b Safety run-in 3 4
Phase 2 63 97
Completed 1 [1] 8 [1]
Not Completed 65 93
Reason Not Completed
Radiological Disease Progression             45             56
Clinical Disease Progression             5             12
Adverse Event             7             11
Withdrawal by Subject             0             4
Subject Choice             2             6
Treatment Completed as per Protocol             3             1
Other             3             3
[1]
Treatment ongoing at data cutoff.
Arm/Group Title Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Total
Hide Arm/Group Description Participants with mTNBC who were never treated with systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1. Participants with mTNBC previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 2. Total of all reporting groups
Overall Number of Baseline Participants 66 101 167
Hide Baseline Analysis Population Description
The full analysis set included all participants who received any amount of either of the study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 66 participants 101 participants 167 participants
55.2  (10.88) 55.6  (11.58) 55.4  (11.28)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 101 participants 167 participants
Female
66
 100.0%
101
 100.0%
167
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 101 participants 167 participants
Hispanic or Latino
3
   4.5%
7
   6.9%
10
   6.0%
Not Hispanic or Latino
63
  95.5%
93
  92.1%
156
  93.4%
Unknown or Not Reported
0
   0.0%
1
   1.0%
1
   0.6%
Asian
0
   0.0%
1
   1.0%
1
   0.6%
Black or African American
7
  10.6%
12
  11.9%
19
  11.4%
White
55
  83.3%
86
  85.1%
141
  84.4%
Other
4
   6.1%
2
   2.0%
6
   3.6%
1.Primary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR was defined as percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) using independent imaging review (IIR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. BOR of CR and PR was confirmed by a subsequent CR assessment and CR or PR assessment, respectively at least 4 weeks later. CR: disappearance of all measurable, non-measurable lesions and no unequivocal new lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD and there are no unequivocal new lesions, and no progression of non-target disease. The 2-sided 95% confidence interval (CI) calculated by Clopper-Pearson method.
Time Frame From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first or up to data cutoff date of 31 July 2019 (up to approximately 3 years 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The evaluable analysis set included all participants who received any amount of either of the study drug and treated at RP2D level who had both an evaluable baseline tumor assessment and an evaluable postbaseline tumor assessment, unless discontinued early or death.
Arm/Group Title Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Hide Arm/Group Description:
Participants with mTNBC who were never treated with systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1.
Participants with mTNBC previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 2.
Participants with mTNBC who were never treated with systemic anticancer therapy and previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1 and 2.
Overall Number of Participants Analyzed 66 101 167
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participant
25.8
(15.8 to 38.0)
21.8
(14.2 to 31.1)
23.4
(17.2 to 30.5)
2.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS was assessed by IIR based on RECIST 1.1. PFS was defined as the time from the date of the first dose of study drug to the date of the first documentation of disease progression or death, whichever occurred first. Progressive disease (PD) for target lesion, a minimum 20% increase and a minimum 5 mm absolute increase in SOD compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir: Lowest measure SOD of target lesion at any time point from baseline onward. The median was calculated by Kaplan-Meier (K-M) method and 95% CI were based on a generalized Brookmeyer and Crowley method.
Time Frame From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first or up to data cutoff date of 31 July 2019 (up to approximately 3 years 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all participants who received any amount of either of the study drug.
Arm/Group Title Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Hide Arm/Group Description:
Participants with mTNBC who were never treated with systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1.
Participants with mTNBC previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 2.
Participants with mTNBC who were never treated with systemic anticancer therapy and previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1 and 2.
Overall Number of Participants Analyzed 66 101 167
Median (95% Confidence Interval)
Unit of Measure: months
4.2
(3.5 to 5.5)
4.1
(2.3 to 4.4)
4.1
(3.5 to 4.2)
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from the date of the first dose of study drug until the date of death from any cause. Median was estimated by K-M method, and the 95% CIs were based on a generalized Brookmeyer and Crowley method.
Time Frame From date of first dose of study drug administration until date of death from any cause or up to data cutoff date of 31 July 2019 (up to approximately 3 years 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all participants who received any amount of either of the study drug.
Arm/Group Title Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Hide Arm/Group Description:
Participants with mTNBC who were never treated with systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1.

Participants with mTNBC previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 2.

.

Participants with mTNBC who were never treated with systemic anticancer therapy and previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1 and 2.
Overall Number of Participants Analyzed 66 101 167
Median (95% Confidence Interval)
Unit of Measure: months
17.4
(13.2 to 21.0)
15.5
(12.5 to 18.7)
16.1
(13.3 to 18.5)
4.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR: time from date of confirmed OR was first documented to date of PD/death due to any cause with confirmed PR/CR using IIR as per RECIST 1.1. BOR of CR and PR was confirmed by subsequent CR assessment and CR or PR assessment, respectively at least 4 weeks later. CR: disappearance of all measurable, non-measurable lesions and no unequivocal new lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR: at least 30%decrease in SOD of target lesions, taking as reference the baseline SOD, there are no unequivocal new lesions, and no progression of non-target disease. PD for target lesion, a minimum 20% increase and a minimum 5 mm absolute increase in SOD compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir: Lowest measure SOD of target lesions at any time point from baseline onward. Median calculated by K-M, 95% CI using Brookmeyer, Crowley method.
Time Frame From the date that a confirmed objective response (OR) was first documented to the date of PD or death due to any cause for those participants with a confirmed PR or CR or up to data cutoff date of 31 July 2019 (up to approximately 3 years 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes all participants who received any amount of either of the study drug. Here 'N' (overall number of participants analyzed) included those participants with BOR (CR or PR).
Arm/Group Title Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Hide Arm/Group Description:
Participants with mTNBC who were never treated with systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1.

Participants with mTNBC previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 2.

.

Participants with mTNBC who were never treated with systemic anticancer therapy and previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1 and 2.
Overall Number of Participants Analyzed 17 22 39
Median (95% Confidence Interval)
Unit of Measure: months
9.0
(6.2 to 22.2)
8.6
(6.2 to 25.1)
8.3
(6.5 to 22.2)
5.Secondary Outcome
Title Clinical Benefit Rate (CBR)
Hide Description CBR was defined as the percentage of participant, who had BOR of CR, PR, or durable stable disease (dSD) (>=24 weeks). CBR was assessed by IIR based on RECIST 1.1. BOR of CR and PR was confirmed by a subsequent CR assessment and CR or PR assessment, respectively at least 4 weeks later. CR: disappearance of all measurable, non-measurable lesions and no unequivocal new lesions. Any pathological lymph nodes (target or non-target) to be reduced in short axis to <10 mm. PR: at least a 30% decrease in SOD of target lesions, as reference the baseline SOD and no unequivocal new lesions, and no progression of non-target disease. Stable disease (SD) must be >=8 weeks after first dose date to be considered best overall response. Durable SD: subset of SD with a duration of >=24 weeks after first dose date. The 2-sided 95% CI is computed by the method of Clopper-Pearson.
Time Frame From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first or up to data cutoff date of 31 July 2019 (up to approximately 3 years 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description

The evaluable analysis set included all participants who received any amount of either of the study drug and treated at RP2D level who had both an evaluable baseline tumor assessment and an evaluable postbaseline tumor assessment, unless discontinued early or death.

Reporting Groups

Arm/Group Title Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Hide Arm/Group Description:
Participants with mTNBC who were never treated with systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1.

Participants with mTNBC previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 2.

.

Participants with mTNBC who were never treated with systemic anticancer therapy and previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1 and 2.
Overall Number of Participants Analyzed 66 101 167
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participant
36.4
(24.9 to 49.1)
29.7
(21.0 to 39.6)
32.3
(25.3 to 40.0)
6.Secondary Outcome
Title ORR in the Programmed Death Receptor-Ligand 1 (PD-L1) Positive Set
Hide Description ORR was defined as the percentage of participant with confirmed BOR of CR or PR. ORR in the PD-L1 positive set was assessed by IIR based on RECIST 1.1. BOR of CR and PR was confirmed by a subsequent CR assessment and CR or PR assessment, respectively at least 4 weeks later. CR: disappearance of all measurable, non-measurable lesions and no unequivocal new lesions. Any pathological lymph nodes (target/non-target) to be reduced in short axis to <10 mm. PR: at least a 30% decrease in SOD of target lesions, as reference the baseline SOD and no unequivocal new lesions, and no progression of non-target disease. PD L1 status was 'Positive' if combined positive score (CPS) >=1 and 'Negative' if CPS ˂1. The 2-sided 95% CI was calculated by the method of Clopper-Pearson.
Time Frame From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first or up to data cutoff date of 31 July 2019 (up to approximately 3 years 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The PD-L1 positive set included all participants who received any amount of either of the study drug, had both an evaluable baseline tumor assessment and an evaluable postbaseline tumor assessment, unless discontinued early or death and whose PD-L1 expression level was above the threshold that was to be specified prior to the final analysis.
Arm/Group Title Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Hide Arm/Group Description:
Participants with mTNBC who were never treated with systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1.
Participants with mTNBC previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 2.
Participants with mTNBC who were never treated with systemic anticancer therapy and previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1 and 2.
Overall Number of Participants Analyzed 29 45 74
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participant
34.5
(17.9 to 54.3)
24.4
(12.9 to 39.5)
28.4
(18.5 to 40.1)
7.Secondary Outcome
Title PFS in the PD-L1 Positive Set
Hide Description PFS was defined as the time from the date of the first dose of study drug to the date of the first documentation of disease progression or death, whichever occurred first. PFS in PD-L1 positive set was assessed by IIR based on RECIST 1.1. PD for target lesion, a minimum 20% increase and a minimum 5 mm absolute increase in SOD compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir: Lowest measure SOD of target legions at any time point from baseline onward. The median were calculated by K-M method and 95% CI are based on a generalized Brookmeyer and Crowley method. PD L1 status was 'Positive' if CPS >=1 and 'Negative' if CPS ˂1.
Time Frame From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurs first or up to data cutoff date of 31 July 2019 (up to approximately 3 years 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The PD-L1 positive set included all participants who received any amount of either of the study drug, had both an evaluable baseline tumor assessment and an evaluable postbaseline tumor assessment, unless discontinued early or death and whose PD-L1 expression level was above the threshold that was to be specified prior to the final analysis.
Arm/Group Title Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Hide Arm/Group Description:
Participants with mTNBC who were never treated with systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1.
Participants with mTNBC previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 2.
Participants with mTNBC who were never treated with systemic anticancer therapy and previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1 and 2.
Overall Number of Participants Analyzed 29 45 74
Median (95% Confidence Interval)
Unit of Measure: months
6.1
(4.1 to 10.2)
4.1
(2.1 to 4.8)
4.2
(3.5 to 6.1)
8.Secondary Outcome
Title OS in the PD-L1 Positive Set
Hide Description OS in the PD-L1 positive set was defined as the time from the date of the first dose of study drug until the date of death from any cause. The median was estimated by KM method, and the 95% CIs were based on a generalized Brookmeyer and Crowley method. PD L1 status was 'Positive' if CPS >=1 and 'Negative' if CPS ˂1.
Time Frame From date of first dose of study drug administration until date of death from any cause or up to data cutoff date of 31 July 2019 (up to approximately 3 years 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The PD-L1 positive set included all participants who received any amount of either of the study drug, had both an evaluable baseline tumor assessment and an evaluable postbaseline tumor assessment, unless discontinued early or death and whose PD-L1 expression level was above the threshold that was to be specified prior to the final analysis.
Arm/Group Title Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Hide Arm/Group Description:
Participants with mTNBC who were never treated with systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1.
Participants with mTNBC previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 2.
Participants with mTNBC who were never treated with systemic anticancer therapy and previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1 and 2.
Overall Number of Participants Analyzed 29 45 74
Median (95% Confidence Interval)
Unit of Measure: months
21.0
(8.3 to 29.0)
14.0
(11.0 to 19.4)
16.3
(12.7 to 24.2)
9.Secondary Outcome
Title DOR in the PD-L1 Positive Set
Hide Description DOR: time from date of confirmed OR was first documented to date of PD or death due to any cause with confirmed PR or CR. DOR in PD-L1 positive set was assessed by using IIR as per RECIST 1.1. BOR of CR and PR was confirmed by a subsequent CR assessment and CR or PR assessment, respectively at least 4 weeks later. CR: disappearance of all measurable, non-measurable lesions and no unequivocal new lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR: at least 30%decrease in SOD of target lesions, taking as reference the baseline SOD, there are no unequivocal new lesions, and no progression of non-target disease. PD for target lesion, a minimum 20% increase and a minimum 5 mm absolute increase in SOD compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir: Lowest measure SOD of target lesions at any time point from baseline onward. Median calculated by K-M and 95% CI using Brookmeyer, Crowley method.
Time Frame From the date that a confirmed objective response is first documented to the date of PD or death due to any cause for those participants with a confirmed PR or CR or up to data cutoff date of 31 July 2019 (up to approximately 3 years 11 months)
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Hide Analysis Population Description
PD-L1 positive set:participants who received any amount of either of study drug, had both an evaluable baseline and postbaseline tumor assessment, unless discontinued early/death,whose PD-L1 expression level was above threshold that was to be specified prior to final analysis.'N'(Overall number of participants analyzed) had participants with CR/PR.
Arm/Group Title Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Hide Arm/Group Description:
Participants with mTNBC who were never treated with systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1.
Participants with mTNBC previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 2.
Participants with mTNBC who were never treated with systemic anticancer therapy and previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1 and 2.
Overall Number of Participants Analyzed 10 11 21
Median (95% Confidence Interval)
Unit of Measure: months
8.3 [1] 
(3.2 to NA)
8.2
(5.1 to 25.1)
8.2
(6.2 to 25.1)
[1]
The upper limit of the 95% CI was not estimable due to the upper side of inequality is not satisfied based on Brookmeyer and Crowley method.
10.Other Pre-specified Outcome
Title CBR in the PD-L1 Positive Set
Hide Description CBR was defined as percentage of participant, had BOR of CR, PR, or dSD (>=24 weeks). CBR in PD-L1 positive set was assessed by IIR based on RECIST 1.1. BOR of CR and PR was confirmed by a subsequent CR assessment and CR or PR assessment, respectively at least 4 weeks later. CR: disappearance of all measurable, non-measurable lesions and no unequivocal new lesions. Any pathological lymph nodes (target or non-target) to be reduced in short axis to<10 mm. PR: at least 30 % decrease in SOD of target lesions, as reference the baseline SOD and no unequivocal new lesions, no progression of non-target disease.SD must be >=8 weeks after first dose date considered best overall response. Durable SD: subset of SD with duration of >=24 weeks after first dose date. The 2 -sided 95% CI is computed by method of Clopper-Pearson. PD L1 status was 'Positive' if CPS>=1, 'Negative' if CPS˂1.
Time Frame From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first or up to data cutoff date of 31 July 2019 (up to approximately 3 years 11 months)
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Hide Analysis Population Description
The PD-L1 positive set included all participants who received any amount of either of the study drug, had both an evaluable baseline tumor assessment and an evaluable postbaseline tumor assessment, unless discontinued early or death and whose PD-L1 expression level was above the threshold that was to be specified prior to the final analysis.
Arm/Group Title Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Hide Arm/Group Description:
Participants with mTNBC who were never treated with systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1.
Participants with mTNBC previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 2.
Participants with mTNBC who were never treated with systemic anticancer therapy and previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1 and 2.
Overall Number of Participants Analyzed 29 45 74
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participant
48.3
(29.4 to 67.5)
28.9
(16.4 to 44.3)
36.5
(25.6 to 48.5)
Time Frame From the first dose of study drug up to 90 days after last dose of study drug, or until resolution, or the start of new anticancer therapy, whichever came first or up to data cutoff date of 31 July 2019 (up to approximately 3 years 11 months)
Adverse Event Reporting Description Safety data is reported based on Stratums 1 and 2, and collectively for combined population participants, as planned.
 
Arm/Group Title Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Hide Arm/Group Description Participants with mTNBC who were never treated with systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1.

Participants with mTNBC previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 2.

.

Participants with mTNBC who were never treated with systemic anticancer therapy and previously treated with 1 to 2 lines of systemic anticancer therapy in the metastatic setting received eribulin mesylate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and pembrolizumab 200 mg, intravenous infusion on Day 1 in Treatment Cycle 1 (safety run-in, Phase 1b) and then continued in each 21-days Treatment Cycles in the presence of clinical benefit until confirmed disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor (up to 41.6 months) in Phase 2 in the Stratum 1 and 2.
All-Cause Mortality
Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   58/66 (87.88%)   62/101 (61.39%)   120/167 (71.86%) 
Hide Serious Adverse Events
Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   30/66 (45.45%)   54/101 (53.47%)   84/167 (50.30%) 
Blood and lymphatic system disorders       
Anaemia  1  1/66 (1.52%)  1/101 (0.99%)  2/167 (1.20%) 
Febrile neutropenia  1  1/66 (1.52%)  3/101 (2.97%)  4/167 (2.40%) 
Neutropenia  1  2/66 (3.03%)  3/101 (2.97%)  5/167 (2.99%) 
Cardiac disorders       
Cardiac arrest  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Pericardial effusion  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Endocrine disorders       
Adrenal insufficiency  1  1/66 (1.52%)  1/101 (0.99%)  2/167 (1.20%) 
Eye disorders       
Retinal detachment  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Gastrointestinal disorders       
Abdominal pain upper  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Colitis  1  1/66 (1.52%)  1/101 (0.99%)  2/167 (1.20%) 
Constipation  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Diarrhoea  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Duodenal ulcer  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Duodenitis  1  0/66 (0.00%)  2/101 (1.98%)  2/167 (1.20%) 
Enteritis  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Gastric ulcer  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Gastritis  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Nausea  1  0/66 (0.00%)  3/101 (2.97%)  3/167 (1.80%) 
Oesophagitis  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Pancreatitis  1  1/66 (1.52%)  1/101 (0.99%)  2/167 (1.20%) 
Stomatitis  1  1/66 (1.52%)  2/101 (1.98%)  3/167 (1.80%) 
Vomiting  1  0/66 (0.00%)  3/101 (2.97%)  3/167 (1.80%) 
General disorders       
Asthenia  1  0/66 (0.00%)  3/101 (2.97%)  3/167 (1.80%) 
Axillary pain  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Death  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Fatigue  1  0/66 (0.00%)  2/101 (1.98%)  2/167 (1.20%) 
Influenza like illness  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Multiple organ dysfunction syndrome  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Pyrexia  1  2/66 (3.03%)  4/101 (3.96%)  6/167 (3.59%) 
Immune system disorders       
Contrast media allergy  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Haemophagocytic lymphohistiocytosis  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Infections and infestations       
Breast cellulitis  1  0/66 (0.00%)  2/101 (1.98%)  2/167 (1.20%) 
Cellulitis  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Device related infection  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Herpes zoster  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Lung infection  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Oesophageal candidiasis  1  1/66 (1.52%)  1/101 (0.99%)  2/167 (1.20%) 
Pneumonia  1  3/66 (4.55%)  5/101 (4.95%)  8/167 (4.79%) 
Sepsis  1  1/66 (1.52%)  2/101 (1.98%)  3/167 (1.80%) 
Septic shock  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Viral myositis  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Wound infection  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Injury, poisoning and procedural complications       
Infusion related reaction  1  2/66 (3.03%)  2/101 (1.98%)  4/167 (2.40%) 
Wound complication  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Investigations       
Alanine aminotransferase increased  1  3/66 (4.55%)  0/101 (0.00%)  3/167 (1.80%) 
Aspartate aminotransferase increased  1  3/66 (4.55%)  0/101 (0.00%)  3/167 (1.80%) 
Blood creatinine increased  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Neutrophil count decreased  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Weight decreased  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Metabolism and nutrition disorders       
Dehydration  1  0/66 (0.00%)  2/101 (1.98%)  2/167 (1.20%) 
Diabetic ketoacidosis  1  1/66 (1.52%)  1/101 (0.99%)  2/167 (1.20%) 
Electrolyte imbalance  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Hyperglycaemia  1  0/66 (0.00%)  2/101 (1.98%)  2/167 (1.20%) 
Hypokalaemia  1  0/66 (0.00%)  2/101 (1.98%)  2/167 (1.20%) 
Hyponatraemia  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Hypophagia  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Type 1 diabetes mellitus  1  1/66 (1.52%)  1/101 (0.99%)  2/167 (1.20%) 
Musculoskeletal and connective tissue disorders       
Arthritis  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Back pain  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Flank pain  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Musculoskeletal pain  1  0/66 (0.00%)  2/101 (1.98%)  2/167 (1.20%) 
Pain in extremity  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cancer pain  1  0/66 (0.00%)  2/101 (1.98%)  2/167 (1.20%) 
Cardiac valve fibroelastoma  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Malignant neoplasm progression  1  0/66 (0.00%)  4/101 (3.96%)  4/167 (2.40%) 
Malignant pleural effusion  1  1/66 (1.52%)  2/101 (1.98%)  3/167 (1.80%) 
Metastases to central nervous system  1  0/66 (0.00%)  2/101 (1.98%)  2/167 (1.20%) 
Metastases to meninges  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Pericardial effusion malignant  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Tumour associated fever  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Nervous system disorders       
Brain oedema  1  1/66 (1.52%)  1/101 (0.99%)  2/167 (1.20%) 
Central nervous system lesion  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Cerebrovascular accident  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Metabolic encephalopathy  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Neurological symptom  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Seizure  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Subdural hygroma  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Transient ischaemic attack  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Renal and urinary disorders       
Acute kidney injury  1  1/66 (1.52%)  1/101 (0.99%)  2/167 (1.20%) 
Nephritis  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Nephrolithiasis  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Ureteric obstruction  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Urinary tract obstruction  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure  1  1/66 (1.52%)  2/101 (1.98%)  3/167 (1.80%) 
Aspiration  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Dyspnoea  1  0/66 (0.00%)  3/101 (2.97%)  3/167 (1.80%) 
Hypoxia  1  0/66 (0.00%)  2/101 (1.98%)  2/167 (1.20%) 
Oropharyngeal pain  1  0/66 (0.00%)  1/101 (0.99%)  1/167 (0.60%) 
Pleural effusion  1  0/66 (0.00%)  2/101 (1.98%)  2/167 (1.20%) 
Pneumonitis  1  3/66 (4.55%)  3/101 (2.97%)  6/167 (3.59%) 
Pulmonary embolism  1  0/66 (0.00%)  2/101 (1.98%)  2/167 (1.20%) 
Respiratory failure  1  2/66 (3.03%)  2/101 (1.98%)  4/167 (2.40%) 
Skin and subcutaneous tissue disorders       
Lichenoid keratosis  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Rash generalised  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Rash maculo-papular  1  1/66 (1.52%)  1/101 (0.99%)  2/167 (1.20%) 
Vascular disorders       
Deep vein thrombosis  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Embolism venous  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Hypotension  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
Subclavian vein thrombosis  1  1/66 (1.52%)  0/101 (0.00%)  1/167 (0.60%) 
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Stratum 1: Eribulin Mesylate + Pembrolizumab Stratum 2: Eribulin Mesylate + Pembrolizumab Overall: Eribulin Mesylate + Pembrolizumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   66/66 (100.00%)   100/101 (99.01%)   166/167 (99.40%) 
Blood and lymphatic system disorders       
Anaemia  1  23/66 (34.85%)  24/101 (23.76%)  47/167 (28.14%) 
Neutropenia  1  19/66 (28.79%)  39/101 (38.61%)  58/167 (34.73%) 
Thrombocytopenia  1  0/66 (0.00%)  7/101 (6.93%)  7/167 (4.19%) 
Endocrine disorders       
Hyperthyroidism  1  7/66 (10.61%)  6/101 (5.94%)  13/167 (7.78%) 
Hypothyroidism  1  16/66 (24.24%)  14/101 (13.86%)  30/167 (17.96%) 
Eye disorders       
Dry eye  1  2/66 (3.03%)  7/101 (6.93%)  9/167 (5.39%) 
Lacrimation increased  1  6/66 (9.09%)  8/101 (7.92%)  14/167 (8.38%) 
Vision blurred  1  4/66 (6.06%)  7/101 (6.93%)  11/167 (6.59%) 
Gastrointestinal disorders       
Abdominal distension  1  4/66 (6.06%)  8/101 (7.92%)  12/167 (7.19%) 
Abdominal pain  1  9/66 (13.64%)  15/101 (14.85%)  24/167 (14.37%) 
Abdominal pain upper  1  5/66 (7.58%)  7/101 (6.93%)  12/167 (7.19%) 
Constipation  1  29/66 (43.94%)  32/101 (31.68%)  61/167 (36.53%) 
Diarrhoea  1  19/66 (28.79%)  32/101 (31.68%)  51/167 (30.54%) 
Dry mouth  1  11/66 (16.67%)  15/101 (14.85%)  26/167 (15.57%) 
Dyspepsia  1  11/66 (16.67%)  10/101 (9.90%)  21/167 (12.57%) 
Gastrooesophageal reflux disease  1  5/66 (7.58%)  6/101 (5.94%)  11/167 (6.59%) 
Nausea  1  45/66 (68.18%)  51/101 (50.50%)  96/167 (57.49%) 
Stomatitis  1  7/66 (10.61%)  25/101 (24.75%)  32/167 (19.16%) 
Vomiting  1  18/66 (27.27%)  25/101 (24.75%)  43/167 (25.75%) 
General disorders       
Asthenia  1  5/66 (7.58%)  7/101 (6.93%)  12/167 (7.19%) 
Chills  1  9/66 (13.64%)  9/101 (8.91%)  18/167 (10.78%) 
Fatigue  1  48/66 (72.73%)  62/101 (61.39%)  110/167 (65.87%) 
Influenza like illness  1  4/66 (6.06%)  6/101 (5.94%)  10/167 (5.99%) 
Non-cardiac chest pain  1  1/66 (1.52%)  8/101 (7.92%)  9/167 (5.39%) 
Oedema peripheral  1  8/66 (12.12%)  7/101 (6.93%)  15/167 (8.98%) 
Pyrexia  1  22/66 (33.33%)  29/101 (28.71%)  51/167 (30.54%) 
Infections and infestations       
Upper respiratory tract infection  1  8/66 (12.12%)  8/101 (7.92%)  16/167 (9.58%) 
Urinary tract infection  1  9/66 (13.64%)  18/101 (17.82%)  27/167 (16.17%) 
Oral candidiasis  1  4/66 (6.06%)  3/101 (2.97%)  7/167 (4.19%) 
Sinusitis  1  2/66 (3.03%)  6/101 (5.94%)  8/167 (4.79%) 
Injury, poisoning and procedural complications       
Fall  1  3/66 (4.55%)  8/101 (7.92%)  11/167 (6.59%) 
Investigations       
Alanine aminotransferase increased  1  15/66 (22.73%)  11/101 (10.89%)  26/167 (15.57%) 
Aspartate aminotransferase increased  1  15/66 (22.73%)  14/101 (13.86%)  29/167 (17.37%) 
Blood alkaline phosphatase increased  1  3/66 (4.55%)  9/101 (8.91%)  12/167 (7.19%) 
Blood creatinine increased  1  3/66 (4.55%)  6/101 (5.94%)  9/167 (5.39%) 
Neutrophil count decreased  1  9/66 (13.64%)  12/101 (11.88%)  21/167 (12.57%) 
Platelet count decreased  1  4/66 (6.06%)  5/101 (4.95%)  9/167 (5.39%) 
Weight decreased  1  20/66 (30.30%)  21/101 (20.79%)  41/167 (24.55%) 
White blood cell count decreased  1  6/66 (9.09%)  13/101 (12.87%)  19/167 (11.38%) 
Metabolism and nutrition disorders       
Decreased appetite  1  29/66 (43.94%)  23/101 (22.77%)  52/167 (31.14%) 
Dehydration  1  10/66 (15.15%)  16/101 (15.84%)  26/167 (15.57%) 
Hyperglycaemia  1  3/66 (4.55%)  8/101 (7.92%)  11/167 (6.59%) 
Hypoalbuminaemia  1  1/66 (1.52%)  9/101 (8.91%)  10/167 (5.99%) 
Hypokalaemia  1  15/66 (22.73%)  12/101 (11.88%)  27/167 (16.17%) 
Hypomagnesaemia  1  5/66 (7.58%)  12/101 (11.88%)  17/167 (10.18%) 
Hyponatraemia  1  6/66 (9.09%)  12/101 (11.88%)  18/167 (10.78%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  24/66 (36.36%)  22/101 (21.78%)  46/167 (27.54%) 
Back pain  1  5/66 (7.58%)  19/101 (18.81%)  24/167 (14.37%) 
Bone pain  1  5/66 (7.58%)  4/101 (3.96%)  9/167 (5.39%) 
Flank pain  1  3/66 (4.55%)  6/101 (5.94%)  9/167 (5.39%) 
Muscle spasms  1  9/66 (13.64%)  6/101 (5.94%)  15/167 (8.98%) 
Muscular weakness  1  5/66 (7.58%)  5/101 (4.95%)  10/167 (5.99%) 
Musculoskeletal pain  1  12/66 (18.18%)  7/101 (6.93%)  19/167 (11.38%) 
Myalgia  1  11/66 (16.67%)  9/101 (8.91%)  20/167 (11.98%) 
Neck pain  1  7/66 (10.61%)  4/101 (3.96%)  11/167 (6.59%) 
Pain in extremity  1  10/66 (15.15%)  14/101 (13.86%)  24/167 (14.37%) 
Arthritis  1  5/66 (7.58%)  0/101 (0.00%)  5/167 (2.99%) 
Joint swelling  1  5/66 (7.58%)  1/101 (0.99%)  6/167 (3.59%) 
Musculoskeletal chest pain  1  4/66 (6.06%)  4/101 (3.96%)  8/167 (4.79%) 
Nervous system disorders       
Dizziness  1  13/66 (19.70%)  14/101 (13.86%)  27/167 (16.17%) 
Dysgeusia  1  6/66 (9.09%)  8/101 (7.92%)  14/167 (8.38%) 
Headache  1  22/66 (33.33%)  19/101 (18.81%)  41/167 (24.55%) 
Hypoaesthesia  1  7/66 (10.61%)  3/101 (2.97%)  10/167 (5.99%) 
Paraesthesia  1  4/66 (6.06%)  5/101 (4.95%)  9/167 (5.39%) 
Peripheral sensory neuropathy  1  35/66 (53.03%)  34/101 (33.66%)  69/167 (41.32%) 
Taste disorder  1  6/66 (9.09%)  3/101 (2.97%)  9/167 (5.39%) 
Memory impairment  1  4/66 (6.06%)  2/101 (1.98%)  6/167 (3.59%) 
Psychiatric disorders       
Anxiety  1  6/66 (9.09%)  7/101 (6.93%)  13/167 (7.78%) 
Depression  1  6/66 (9.09%)  7/101 (6.93%)  13/167 (7.78%) 
Insomnia  1  11/66 (16.67%)  11/101 (10.89%)  22/167 (13.17%) 
Reproductive system and breast disorders       
Breast pain  1  4/66 (6.06%)  4/101 (3.96%)  8/167 (4.79%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  24/66 (36.36%)  30/101 (29.70%)  54/167 (32.34%) 
Dyspnoea  1  16/66 (24.24%)  23/101 (22.77%)  39/167 (23.35%) 
Nasal congestion  1  9/66 (13.64%)  9/101 (8.91%)  18/167 (10.78%) 
Oropharyngeal pain  1  7/66 (10.61%)  7/101 (6.93%)  14/167 (8.38%) 
Pneumonitis  1  4/66 (6.06%)  9/101 (8.91%)  13/167 (7.78%) 
Dysphonia  1  4/66 (6.06%)  1/101 (0.99%)  5/167 (2.99%) 
Dyspnoea exertional  1  5/66 (7.58%)  2/101 (1.98%)  7/167 (4.19%) 
Pulmonary embolism  1  4/66 (6.06%)  1/101 (0.99%)  5/167 (2.99%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  35/66 (53.03%)  31/101 (30.69%)  66/167 (39.52%) 
Pruritus  1  9/66 (13.64%)  12/101 (11.88%)  21/167 (12.57%) 
Rash  1  16/66 (24.24%)  15/101 (14.85%)  31/167 (18.56%) 
Rash maculo-papular  1  9/66 (13.64%)  9/101 (8.91%)  18/167 (10.78%) 
Hyperhidrosis  1  4/66 (6.06%)  0/101 (0.00%)  4/167 (2.40%) 
Vascular disorders       
Hot flush  1  10/66 (15.15%)  11/101 (10.89%)  21/167 (12.57%) 
Hypertension  1  2/66 (3.03%)  9/101 (8.91%)  11/167 (6.59%) 
Hypotension  1  4/66 (6.06%)  4/101 (3.96%)  8/167 (4.79%) 
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Eisai Medical Information
Organization: Eisai Inc.
Phone: 1-888-274-2378
EMail: esi_oncmedinfo@eisai.com
Layout table for additonal information
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT02513472    
Other Study ID Numbers: E7389-M001-218
KEYNOTE-150 ( Other Identifier: Merck Sharp and Dohme Corp )
First Submitted: July 29, 2015
First Posted: July 31, 2015
Results First Submitted: July 29, 2020
Results First Posted: August 14, 2020
Last Update Posted: August 14, 2020