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

NCT ID: NCT02447003

Last Updated: 2020-12-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 254 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-11
• Study Completion Date: 2020-01-31

Brief Summary

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.

Detailed 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.

Conditions

Breast Cancer

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: Pembrolizumab

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).

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

IV infusion of 200 mg.

Cohort B: Pembrolizumab

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).

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

IV infusion of 200 mg.

Interventions

Pembrolizumab

IV infusion of 200 mg.

Intervention Type: BIOLOGICAL

Other Intervention Names

MK-3475; KEYTRUDA®

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Countries

Australia; Belgium; Canada; France; Germany; Israel; Italy; Japan; New Zealand; Puerto Rico; South Africa; Spain; United Kingdom; United States

References

Loi S, Salgado R, Schmid P, Cortes J, Cescon DW, Winer EP, Toppmeyer DL, Rugo HS, De Laurentiis M, Nanda R, Iwata H, Awada A, Tan AR, Sun Y, Karantza V, Wang A, Huang L, Saadatpour A, Cristescu R, Yearley J, Lunceford J, Jelinic P, Adams S. Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis. JCO Precis Oncol. 2023 Apr;7:e2200317. doi: 10.1200/PO.22.00317.

Reference Type: DERIVED

PMID: 37099733 (View on PubMed)

Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.

Reference Type: DERIVED

PMID: 35101941 (View on PubMed)

Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, Cescon DW, Iwata H, Campone M, Nanda R, Hui R, Curigliano G, Toppmeyer D, O'Shaughnessy J, Loi S, Paluch-Shimon S, Tan AR, Card D, Zhao J, Karantza V, Cortes J. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study. Ann Oncol. 2019 Mar 1;30(3):397-404. doi: 10.1093/annonc/mdy517.

Reference Type: DERIVED

PMID: 30475950 (View on PubMed)

Adams S, Loi S, Toppmeyer D, Cescon DW, De Laurentiis M, Nanda R, Winer EP, Mukai H, Tamura K, Armstrong A, Liu MC, Iwata H, Ryvo L, Wimberger P, Rugo HS, Tan AR, Jia L, Ding Y, Karantza V, Schmid P. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol. 2019 Mar 1;30(3):405-411. doi: 10.1093/annonc/mdy518.

Reference Type: DERIVED

PMID: 30475947 (View on PubMed)

Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol. 2016 Jul 20;34(21):2460-7. doi: 10.1200/JCO.2015.64.8931. Epub 2016 May 2.

Reference Type: DERIVED

PMID: 27138582 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://merckoncologyclinicaltrials.com

Merck Oncology Clinical Trial Information

Other Identifiers

2015-000294-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

152987

Identifier Type: REGISTRY

Identifier Source: secondary_id

3475-086

Identifier Type: -

Identifier Source: org_study_id