Abstract 356TiP
Background
First-line (1L) combination treatment with pembrolizumab (pembro) + chemotherapy (chemo) improved PFS in patients with PD-L1+ metastatic triple-negative breast cancer (TNBC) compared with chemo alone (KEYNOTE-355). However, tolerable and effective maintenance regimens after induction therapy are needed to sustain clinical benefit. The PARP inhibitor olaparib is an established maintenance therapy in multiple platinum-sensitive tumor types, and previous data suggest that olaparib combined with the PD-1 inhibitor pembro may have an improved therapeutic effect. Here we present the study design for KEYLYNK-009 (NCT04191135), a phase II/III, open-label, randomized study of pembro + olaparib or pembro + chemo in patients with locally recurrent inoperable or metastatic TNBC who showed clinical benefit after induction with 1L pembro + chemo.
Trial design
Patients with measurable, locally recurrent, inoperable or metastatic TNBC that has not been previously treated with chemo in the metastatic setting and cannot be treated with curative intent will enroll in this 2-in-1 study design (n=∼317; phase II); if the planned efficacy boundary is met, ∼615 additional patients will be enrolled (phase III). All patients will receive induction therapy for up to 6 cycles of pembro 200 mg every 3 wk (Q3W) + chemo (carboplatin AUC 2 + gemcitabine 1000 mg/m2). Patients will be eligible for postinduction treatment if they achieve complete or partial response or maintain stable disease during induction after 4-6 treatment cycles. These patients will be randomized 1:1 to receive pembro 200 mg Q3W + olaparib 300 mg twice daily or continue pembro + chemo (same as induction regimen). Olaparib and chemo may continue until progression or unacceptable toxicity; pembro may continue for ≤35 cycles (including induction), unacceptable toxicity, or progression. Dual primary endpoints for phase III are PFS per RECIST v1.1 by BICR and OS. Secondary endpoints include OS and PFS in patients with BRCAm, health-related quality of life, and safety. Enrollment is ongoing.
Clinical trial identification
NCT04191135.
Editorial acknowledgement
Medical writing and editorial assistance were provided by Lindsay Grant, PhD, and Jenna Lewis, MA, ELS, MedThink SciCom. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. The authors would like to acknowledge Jing Zhao for her contributions to the abstract.
Legal entity responsible for the study
The authors.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
H.S. Rugo: Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution): Novartis; Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): OBI; Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): Immunomedics; Travel/Accommodation/Expenses: Mylan; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Puma; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Celtrion. F. André: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Daiichi ; Research grant/Funding (institution): Roche. S. Saji: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Chugai; Honoraria (self), Research grant/Funding (self): Eisai; Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Takeda; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy: Kyowa-Kirin; Honoraria (self): MSD; Honoraria (self): Pfizer; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): Taiho Pharmaceutical. N. Harbeck: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Roche. P. Schmid: Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Celgene; Advisory/Consultancy: Daiichi-Sankyo; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Eisai; Advisory/Consultancy: Eli Lilly. D.W. Cescon: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genomic Health; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Agendia; Advisory/Consultancy: Dynamo Therapeutics. L. Fan: Full/Part-time employment: Merck & Co., Inc. J. Mejia: Full/Part-time employment: Merck & Co., Inc. V. Karantza: Full/Part-time employment: Merck & Co., Inc. All other authors have declared no conflicts of interest.