Abstract OT1-03-20: A phase 2 study of pembrolizumab (MK-3475) monotherapy for metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086
Authors: Adams S , Card D , Zhao J , Karantza V , Aktan G 
Published: May 2016

Abstract
Background: TNBC is defined by a lack of ER and PR expression and the absence of HER2 overexpression. As such, the only approved systemic treatment option approved for mTNBC is chemotherapy, which is associated with median survival of &lt;1 year. The programmed death receptor 1 (PD-1) pathway is frequently altered in cancer and used by tumors to evade an immune response. Pembrolizumab, an anti–PD-1 monoclonal antibody that prevents PD-1 from binding to its ligands, PD-L1 and PD-L2, has shown durable antitumor activity and a manageable toxicity profile in many advanced cancers, including mTNBC. In the phase 1b KEYNOTE-012 study, pembrolizumab 10 mg/kg given every 2 weeks (Q2W) provided an ORR of 18.5% and a 6-month PFS rate of 24.4% (RECIST v1.1, central review) in a cohort of 32 heavily pretreated patients with PD-L1–positive mTNBC.
Trial Design: KEYNOTE-086 is a 2-part, multicohort, nonrandomized, phase 2 trial of pembrolizumab monotherapy for women and men with mTNBC (ClinicalTrials.gov, NCT02447003). Key eligibility for all cohorts include age ≥18 years, centrally determined mTNBC, ECOG PS 0 or 1, measurable disease per RECIST v1.1 by central review, and provision of a tumor sample for assessment of ER, PR, HER2, and PD-L1 status at a central laboratory. PD-L1 expression will be assessed by immunohistochemistry using the 22C3 antibody (Merck), with positivity defined as PD-L1 expression in the stroma or in ≥1% of tumor cells. Part 1 includes 2 cohorts that will enroll simultaneously. In cohort A, up to 160 pts with any PD-L1 status who have received ≥1 systemic treatment for metastatic breast cancer, were treated with an anthracycline and a taxane in the (neo)adjuvant and/or metastatic setting, and had documented disease progression on their most recent therapy will be enrolled. In cohort B, up to 40 pts with PD-L1–positive tumors who have received no prior systemic therapy for metastatic breast cancer will be enrolled. Part 2 is an expansion cohort of cohort A that will enroll up to 45 pts with tumors strongly positive for PD-L1 expression; part 2 will be initiated only if ≥1 response is observed in the cohort A PD-L1-strong-positive population. The definition of strongly positive PD-L1 expression will be determined in part 1. In all cohorts, pts will receive pembrolizumab 200 mg Q3W for 24 mo or until disease progression, intolerable toxicity, or patient or investigator decision. Clinically stable pts may continue pembrolizumab beyond initial RECIST-defined progression. Response will be assessed per RECIST v1.1 by central review every 9 wk for the first 12 mo and every 12 wk thereafter. AEs will be monitored throughout treatment and for 30 days thereafter (90 days for serious AEs and events of clinical interest). Primary end point is ORR. Secondary end points include duration of response (DOR), disease control rate, PFS, and OS. Efficacy and safety will be evaluated in all patients who receive ≥1 pembrolizumab dose. The Kaplan-Meier method will be used to estimate DOR, PFS, and OS.
Current Status: Enrollment in KEYNOTE-086 will begin in June 2015 and continue until up to 245 patients are accrued. For additional information on KEYNOTE-086, contact MerckClinTrialSupport@merck.com.
Citation Format: Adams S, Card D, Zhao J, Karantza V, Aktan G. A phase 2 study of pembrolizumab (MK-3475) monotherapy for metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-03-20.