An Open-Label, Single-Arm Multicenter Phase 1b/2 Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Combination With Pembrolizumab in Subjects With Metastatic Triple-Negative Breast Cancer (mTNBC)
Overview
- Phase
- Phase 1
- Intervention
- Eribulin Mesylate
- Conditions
- Breast Neoplasm
- Sponsor
- Eisai Inc.
- Enrollment
- 258
- Locations
- 2
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Females or males, aged \>=18 years at the time of signing the informed consent form (ICF).
- •mTNBC (confirmed from most recent tissue sample) meeting the following criteria:
- •Estrogen receptor (ER) and progesterone receptor negative (a tumor is ER and/or progesterone receptor positive if at least 1 percent (%) of the cells examined have estrogen and/or progesterone receptors) and human epidermal growth factor receptor 2 (HER2) negative (defined as immunohistochemistry \[IHC\] less than (\<) 2+ or fluorescence in situ hybridization \[FISH\] negative).
- •Previously treated with 0 to 2 lines of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting. Hormonal therapy and bone metastases treatment (example, bisphosphonates, denosumab, etc) are not considered forms of systemic anticancer therapy.
- •Presence of measurable disease meeting the following criteria:
- •At least 1 lesion of \>=10 millimeter (mm) in long axis diameter for nonlymph nodes or \>=15 mm in short axis diameter for lymph nodes that is serially measurable according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) using computerized tomography (CT) or magnetic resonance imaging (MRI) or panoramic and close-up color photography.
- •Lesions that have had radiotherapy must show subsequent radiographic evidence of increased size to be deemed a target lesion.
- •Life expectancy of \>=3 months.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or
- •Adequate renal function as evidenced by serum creatinine less than or equal to (\<=) 1.5 milligram per deciliter (mg/dL) or calculated creatinine clearance \>=50 millimeter per minute (mL/min) according to the Cockcroft and Gault formula.
Exclusion Criteria
- •Previous treatment with eribulin mesylate or any anti-programmed death receptor-1 (anti-PD-1), programmed death receptor ligand-1 (PD-L1), or PD-L2 agent.
- •Active autoimmune disease that has required systemic treatment in the past 2 years (that is, with use of disease modifying agents, corticosteroids, or immunosuppresive drugs). Replacement therapy (example, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment.
- •Less than 6 months since prior adjuvant chemotherapy.
- •Current enrollment in another interventional clinical study or used any investigational drug or device within the past 28 days preceding informed consent.
- •Treatment with chemotherapy or biological therapy within the previous 3 weeks, radiation or small molecule targeted therapy within the previous 2 weeks.
- •Known central nervous system (CNS) disease, except for those participants with treated brain metastasis who are stable for at least 1 month, having no evidence of progression or hemorrhage after treatment and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
- •Known history of human immunodeficiency virus (HIV) positive.
- •Known active hepatitis B (example, HBsAg reactive) or hepatitis C (example, hepatitis C virus ribonucleic acid (HCV RNA) detected).
- •Existing anticancer treatment-related toxicities of Grades \>= 2 (except for alopecia and Grade 2 sensory neuropathy) according to Common Terminology Criteria for Adverse Events (CTCAE v4.03).
- •Any other malignancy that required treatment or has shown evidence of recurrence (except for nonmelanoma skin cancer, or histologically confirmed complete excision of carcinoma in situ) during the 5 years prior to enrollment in this study.
Arms & Interventions
Eribulin Mesylate + Pembrolizumab
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.
Intervention: Eribulin Mesylate
Eribulin Mesylate + Pembrolizumab
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.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
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 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.
Secondary Outcomes
- Overall Survival (OS)(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)(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)(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(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)(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(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(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(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))