Study of Pembrolizumab (MK-3475) Monotherapy for Metastatic Triple-Negative Breast Cancer (MK-3475-086/KEYNOTE-086)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Biological: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02447003

2015-000294-13 (EudraCT Number)

152987 (Registry Identifier)

3475-086

Details and patient eligibility

About

This is a two-part study of pembrolizumab monotherapy in participants with metastatic triple-negative breast cancer (mTNBC). Part 1 of the study will examine the efficacy and safety of pembrolizumab monotherapy as first line or above treatment in participants who have received either no prior systemic treatment or at least one prior systemic treatment for metastatic breast cancer. Part 2 of the study, if done, will expand the investigation of pembrolizumab treatment in a subgroup of participants from Part 1 and will only start after enrollment in Part 1 has been completed. There will be no hypothesis testing in this study.

Full description

Qualified participants who complete up to ~2 years of pembrolizumab treatment but progress after discontinuation may be eligible for a second course of pembrolizumab for up to ~1 additional year, at the Investigator's discretion. Per protocol, response or progression during this second course will not count towards efficacy outcome measure and adverse events during this second course will not count towards safety outcome measures.

Enrollment: 254 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

For the purposes of this study, neoadjuvant and/or adjuvant chemotherapy regimens do not count as a prior line of therapy.

For second line plus monotherapy (Parts 1 and 2):

• Has received at least one systemic treatment for metastatic breast cancer
• Has documented disease progression on or after the most recent therapy
• Prior treatment must include an anthracycline and a taxane in the neoadjuvant, adjuvant, or metastatic setting

For first line monotherapy (Part 1):

• Has received no prior systemic treatment for metastatic breast cancer
• Has PD-L1-positive mTNBC.

For second line plus monotherapy (Part 2):

• Has PD-L1 strong positive mTNBC

For all parts:

• Has mTNBC confirmed by a central laboratory
• For biomarker analysis, adequate newly obtained core or excisional biopsy of a not-previously-irradiated metastatic tumor lesion (mandatory)
• Has measurable metastatic disease
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment
• Male participants should agree to use an adequate method of contraception starting with the first dose of study treatment through 120 days after the last dose of study treatment
• Has adequate organ function

Exclusion criteria

• Is currently participating and receiving study treatment, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to study Day 1
• Has received prior anti-cancer monoclonal antibody (mAb) therapy for direct anti-neoplastic treatment within 4 weeks prior to study Day 1
• Has received prior chemotherapy, targeted small molecule therapy, or radiation therapy within at least 2 weeks prior to study Day 1
• Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered within at least 2 weeks prior to study Day 1
• Has an active autoimmune disease requiring systemic treatment in past 2 years
• Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
• Has known additional malignancy that progressed or required active treatment within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
• Has radiographically-detectable central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis or a history of interstitial lung disease
• Has an active infection requiring systemic therapy
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
• Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
• Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein-4 [CTLA-4], OX-40, CD137) or has participated in Merck MK-3475 (pembrolizumab) study
• Has a known history of human immunodeficiency virus (HIV)
• Has known active Hepatitis B or C
• Has received a live vaccine within 30 days of planned start of study treatment

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

254 participants in 2 patient groups

Cohort A: Pembrolizumab

Experimental group

Description:

Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants will be administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to \~ 2 years).

Treatment:

Biological: Pembrolizumab

Cohort B: Pembrolizumab

Experimental group

Description:

Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants will be administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to \~ 2 years).

Treatment:

Biological: Pembrolizumab