This is an open-label, single-arm, multicenter, Phase 1b/2 study of eribulin mesylate in combination with pembrolizumab in participants with mTNBC previously treated with 0 (stratum 1) or 1 to 2 (stratum 2) lines of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting.
The Phase 1b part will evaluate the safety and tolerability of eribulin mesylate in combination with pembrolizumab. Approximately 6 participants may be enrolled in the Phase 1b part of the study. The Phase 2 part will evaluate the tumor objective response rate (ORR) when treated with eribulin mesylate in combination with pembrolizumab in all participants and will also evaluate ORR in stratum 2 participants and compare with the historical response rate of pembrolizumab monotherapy 10 percent (%) in participants with mTNBC previously treated with \>=1 line of prior chemotherapy in the metastatic setting. Approximately 170 mTNBC participants (including participants in Phase 1b who are on RP2D level) will be enrolled in Phase 2.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
258
Eribulin Mesylate will be administered as a 1.4 milligram per square meter (mg/m\^2) IV (intravenous) infusion on Day 1 and Day 8 of each 21-day cycle in the presence of clinical benefit until intercurrent illness, unacceptable toxicity, or disease progression occurs, or until the participant withdraws consent.
Pembrolizumab will be administered as a 200 milligram (mg) IV infusion on Day 1 of each 21-day cycle in the presence of clinical benefit until intercurrent illness, unacceptable toxicity, or disease progression occurs, or until the participant withdraws consent.
Facility #1
Duarte, California, United States
Facility #1
Santa Barbara, California, United States
Objective Response Rate (ORR)
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.
Time frame: 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)
Progression-free Survival (PFS)
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.
Time frame: 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)
Overall Survival (OS)
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.
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Facility #1
Denver, Colorado, United States
Facility #1
Miami, Florida, United States
Facility #1
West Palm Beach, Florida, United States
Facility #1
Boston, Massachusetts, United States
Facility #2
Boston, Massachusetts, United States
Facility #1
Minneapolis, Minnesota, United States
Facility #1
St Louis, Missouri, United States
Facility #1
Lebanon, New Hampshire, United States
...and 12 more locations
Time frame: From date of first dose of study drug administration until date of death from any cause (up to 3 years 11 months)
Duration of Response (DOR)
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.
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 (up to 3 years 11 months)
Clinical Benefit Rate (CBR)
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.
Time frame: 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)
ORR in the Programmed Death Receptor-Ligand 1 (PD-L1) Positive Set
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.
Time frame: 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)
PFS in the PD-L1 Positive Set
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.
Time frame: 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)
OS in the PD-L1 Positive Set
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.
Time frame: From date of first dose of study drug administration until date of death from any cause (up to 3 years 11 months)
DOR in the PD-L1 Positive Set
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 (up to 3 years 11 months)