Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Combination With Pembrolizumab in Participants With Metastatic Triple-Negative Breast Cancer (mTNBC) (NCT NCT02513472)

Last Updated: 2022-05-05

Results Overview

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. As planned, data up to the primary completion date only were analyzed.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

258 participants

Primary outcome timeframe

From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first (up to 3 years 11 months)

Results posted on

2022-05-05

Participant Flow

Participants took part in the study at 18 investigative sites in the United States. A total 258 participants were screened and enrolled, of which 91 were screen failures and 167 were treated. RP2D is recommended Phase 2 dose.

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.

Participant milestones

Participant milestones
Measure	Stratum 1: Eribulin Mesylate + Pembrolizumab 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 in Phase 2 in the Stratum 1.	Stratum 2: Eribulin Mesylate + Pembrolizumab 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 in Phase 2 in the Stratum 2.
Overall Study STARTED	66	101
Overall Study Phase 1b Safety run-in	3	4
Overall Study Phase 2	63	97
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	66	101

Reasons for withdrawal

Reasons for withdrawal
Measure	Stratum 1: Eribulin Mesylate + Pembrolizumab 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 in Phase 2 in the Stratum 1.	Stratum 2: Eribulin Mesylate + Pembrolizumab 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 in Phase 2 in the Stratum 2.
Overall Study Radiological Disease Progression	45	57
Overall Study Clinical Disease Progression	5	13
Overall Study Adverse Event	8	11
Overall Study Withdrawal by Subject	0	4
Overall Study Subject Choice	2	7
Overall Study Treatment Completed as per Protocol	3	3
Overall Study Other	3	6

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stratum 1: Eribulin Mesylate + Pembrolizumab n=66 Participants 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 in Phase 2 in the Stratum 1.	Stratum 2: Eribulin Mesylate + Pembrolizumab n=101 Participants 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 in Phase 2 in the Stratum 2.	Total n=167 Participants Total of all reporting groups
Age, Continuous	55.2 years STANDARD_DEVIATION 10.88 • n=5 Participants	55.6 years STANDARD_DEVIATION 11.58 • n=7 Participants	55.4 years STANDARD_DEVIATION 11.28 • n=5 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	101 Participants n=7 Participants	167 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	63 Participants n=5 Participants	93 Participants n=7 Participants	156 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	7 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized White	55 Participants n=5 Participants	86 Participants n=7 Participants	141 Participants n=5 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first (up to 3 years 11 months)

Population: 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.

Outcome measures

Outcome measures
Measure	Stratum 1: Eribulin Mesylate + Pembrolizumab n=66 Participants 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 in Phase 2 in the Stratum 1.	Stratum 2: Eribulin Mesylate + Pembrolizumab n=101 Participants 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 in Phase 2 in the Stratum 2.	Overall: Eribulin Mesylate + Pembrolizumab n=167 Participants 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 in Phase 2 in the Stratum 1 and 2.
Objective Response Rate (ORR)	25.8 percentage of participant Interval 15.8 to 38.0	21.8 percentage of participant Interval 14.2 to 31.1	23.4 percentage of participant Interval 17.2 to 30.5

SECONDARY outcome

Timeframe: From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first (up to 3 years 11 months)

Population: The full analysis set included all participants who received any amount of either of the study drug.

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. As planned, data up to the primary completion date only were analyzed.

Outcome measures

Outcome measures
Measure	Stratum 1: Eribulin Mesylate + Pembrolizumab n=66 Participants 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 in Phase 2 in the Stratum 1.	Stratum 2: Eribulin Mesylate + Pembrolizumab n=101 Participants 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 in Phase 2 in the Stratum 2.	Overall: Eribulin Mesylate + Pembrolizumab n=167 Participants 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 in Phase 2 in the Stratum 1 and 2.
Progression-free Survival (PFS)	4.2 months Interval 3.5 to 5.5	4.1 months Interval 2.3 to 4.4	4.1 months Interval 3.5 to 4.2

SECONDARY outcome

Timeframe: From date of first dose of study drug administration until date of death from any cause (up to 3 years 11 months)

Population: The full analysis set included all participants who received any amount of either of the study drug.

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. As planned, data up to the primary completion date only were analyzed.

Outcome measures

Outcome measures
Measure	Stratum 1: Eribulin Mesylate + Pembrolizumab n=66 Participants 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 in Phase 2 in the Stratum 1.	Stratum 2: Eribulin Mesylate + Pembrolizumab n=101 Participants 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 in Phase 2 in the Stratum 2.	Overall: Eribulin Mesylate + Pembrolizumab n=167 Participants 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 in Phase 2 in the Stratum 1 and 2.
Overall Survival (OS)	17.4 months Interval 13.2 to 21.0	15.5 months Interval 12.5 to 18.7	16.1 months Interval 13.3 to 18.5

SECONDARY outcome

Timeframe: 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 (up to 3 years 11 months)

Population: 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).

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 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 5mm absolute increase in SOD compared to nadir, or PD for non-target lesions or unequivocal new lesions. 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. As planned, data up to the primary completion date only were analyzed.

Outcome measures

Outcome measures
Measure	Stratum 1: Eribulin Mesylate + Pembrolizumab n=17 Participants 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 in Phase 2 in the Stratum 1.	Stratum 2: Eribulin Mesylate + Pembrolizumab n=22 Participants 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 in Phase 2 in the Stratum 2.	Overall: Eribulin Mesylate + Pembrolizumab n=39 Participants 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 in Phase 2 in the Stratum 1 and 2.
Duration of Response (DOR)	9.0 months Interval 6.2 to 22.2	8.6 months Interval 6.2 to 25.1	8.3 months Interval 6.5 to 22.2

SECONDARY outcome

Timeframe: From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first (up to 3 years 11 months)

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. As planned, data up to the primary completion date only were analyzed.

Outcome measures

Outcome measures
Measure	Stratum 1: Eribulin Mesylate + Pembrolizumab n=66 Participants 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 in Phase 2 in the Stratum 1.	Stratum 2: Eribulin Mesylate + Pembrolizumab n=101 Participants 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 in Phase 2 in the Stratum 2.	Overall: Eribulin Mesylate + Pembrolizumab n=167 Participants 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 in Phase 2 in the Stratum 1 and 2.
Clinical Benefit Rate (CBR)	36.4 percentage of participant Interval 24.9 to 49.1	29.7 percentage of participant Interval 21.0 to 39.6	32.3 percentage of participant Interval 25.3 to 40.0

SECONDARY outcome

Timeframe: From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first (up to 3 years 11 months)

Population: 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.

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. As planned, data up to the primary completion date only were analyzed.

Outcome measures

Outcome measures
Measure	Stratum 1: Eribulin Mesylate + Pembrolizumab n=29 Participants 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 in Phase 2 in the Stratum 1.	Stratum 2: Eribulin Mesylate + Pembrolizumab n=45 Participants 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 in Phase 2 in the Stratum 2.	Overall: Eribulin Mesylate + Pembrolizumab n=74 Participants 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 in Phase 2 in the Stratum 1 and 2.
ORR in the Programmed Death Receptor-Ligand 1 (PD-L1) Positive Set	34.5 percentage of participant Interval 17.9 to 54.3	24.4 percentage of participant Interval 12.9 to 39.5	28.4 percentage of participant Interval 18.5 to 40.1

SECONDARY outcome

Timeframe: From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurs first (up to 3 years 11 months)

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 was 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. As planned, data up to the primary completion date only were analyzed.

Outcome measures

Outcome measures
Measure	Stratum 1: Eribulin Mesylate + Pembrolizumab n=29 Participants 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 in Phase 2 in the Stratum 1.	Stratum 2: Eribulin Mesylate + Pembrolizumab n=45 Participants 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 in Phase 2 in the Stratum 2.	Overall: Eribulin Mesylate + Pembrolizumab n=74 Participants 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 in Phase 2 in the Stratum 1 and 2.
PFS in the PD-L1 Positive Set	6.1 months Interval 4.1 to 10.2	4.1 months Interval 2.1 to 4.8	4.2 months Interval 3.5 to 6.1

SECONDARY outcome

Timeframe: From date of first dose of study drug administration until date of death from any cause (up to 3 years 11 months)

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. As planned, data up to the primary completion date only were analyzed.

Outcome measures

Outcome measures
Measure	Stratum 1: Eribulin Mesylate + Pembrolizumab n=29 Participants 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 in Phase 2 in the Stratum 1.	Stratum 2: Eribulin Mesylate + Pembrolizumab n=45 Participants 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 in Phase 2 in the Stratum 2.	Overall: Eribulin Mesylate + Pembrolizumab n=74 Participants 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 in Phase 2 in the Stratum 1 and 2.
OS in the PD-L1 Positive Set	21.0 months Interval 8.3 to 29.0	14.0 months Interval 11.0 to 19.4	16.3 months Interval 12.7 to 24.2

SECONDARY outcome

Timeframe: 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 (up to 3 years 11 months)

Population: 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. As planned, data up to the primary completion date only were analyzed.

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.

Outcome measures

Outcome measures
Measure	Stratum 1: Eribulin Mesylate + Pembrolizumab n=10 Participants 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 in Phase 2 in the Stratum 1.	Stratum 2: Eribulin Mesylate + Pembrolizumab n=11 Participants 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 in Phase 2 in the Stratum 2.	Overall: Eribulin Mesylate + Pembrolizumab n=21 Participants 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 in Phase 2 in the Stratum 1 and 2.
DOR in the PD-L1 Positive Set	8.3 months Interval 3.2 to 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.	8.2 months Interval 5.1 to 25.1	8.2 months Interval 6.2 to 25.1

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurred first (up to 3 years 11 months)

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. As planned, data up to the primary completion date only were analyzed.

Outcome measures

Outcome measures
Measure	Stratum 1: Eribulin Mesylate + Pembrolizumab n=29 Participants 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 in Phase 2 in the Stratum 1.	Stratum 2: Eribulin Mesylate + Pembrolizumab n=45 Participants 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 in Phase 2 in the Stratum 2.	Overall: Eribulin Mesylate + Pembrolizumab n=74 Participants 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 in Phase 2 in the Stratum 1 and 2.
CBR in the PD-L1 Positive Set	48.3 percentage of participant Interval 29.4 to 67.5	28.9 percentage of participant Interval 16.4 to 44.3	36.5 percentage of participant Interval 25.6 to 48.5

Adverse Events

Stratum 1: Eribulin Mesylate + Pembrolizumab

Serious events: 30 serious events

Other events: 66 other events

Deaths: 59 deaths

Stratum 2: Eribulin Mesylate + Pembrolizumab

Serious events: 57 serious events

Other events: 100 other events

Deaths: 79 deaths

Overall: Eribulin Mesylate + Pembrolizumab

Serious events: 87 serious events

Other events: 166 other events

Deaths: 138 deaths

Serious adverse events

Other adverse events

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: 1-888-274-2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place