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)

• 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: Eisai Inc.
• 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

Participant Flow

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
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.

Baseline Characteristics

Arm/Group Title		Stratum 1: Eribulin Mesylate + Pembrolizumab	Stratum 2: Eribulin Mesylate + Pembrolizumab	Total
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
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%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
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)

Outcome Measure Data

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
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)
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)

Outcome Measure Data

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
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)
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)

Outcome Measure Data

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
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)
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)

Outcome Measure Data

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
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)
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)

Outcome Measure Data

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
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
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)

Outcome Measure Data

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
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
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)

Outcome Measure Data

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
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
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)

Outcome Measure Data

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
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
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)

Outcome Measure Data

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
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
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)

Outcome Measure Data

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
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)

Adverse Events

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
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%)
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
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

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Eisai Medical Information
• Organization: Eisai Inc.
• Phone: 1-888-274-2378
• EMail: esi_oncmedinfo@eisai.com

• 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