Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs. Placebo Plus Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer (MK-3475-355/KEYNOTE-355)
Summary
The study will consist of two parts. In Part 1, the safety of pembrolizumab (MK-3475) in combination with one of three different chemotherapies will be assessed in the treatment of locally recurrent inoperable or metastatic triple negative breast cancer (TNBC), which has not been previously treated with chemotherapy. In Part 2, the safety and efficacy of pembrolizumab plus background chemotherapy will be assessed compared to the safety and efficacy of placebo plus background chemotherapy in the treatment of locally recurrent inoperable or metastatic TNBC, which has not been previously treated with chemotherapy. The primary hypotheses are that: 1. the combination of pembrolizumab and chemotherapy prolongs Progression-Free Survival (PFS) compared to placebo and chemotherapy in: * all participants, * participants with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 tumors, and * participants with PD-L1 CPS ≥10 tumors, and 2. the combination of pembrolizumab and chemotherapy prolongs Overall Survival (OS) compared to placebo and chemotherapy in: * all participants, * participants with PD-L1 CPS ≥1 tumors, and * participants with PD-L1 CPS ≥10 tumors.
Timeline
- Start
- 2016-07-27
- Primary completion
- 2021-06-15
- Completion
- 2023-10-30
Outcome
Mixed primary results
registry analysis (superiority test); Part 2: Pembrolizumab + Chemotherapy vs Part 2: Placebo + Chemotherapy; p = 0.0120; Hazard Ratio (HR) 0.82 (95% CI 0.70 to 0.98); Log Rank; NCT02819518 ↗
registry analysis (superiority test); Part 2: Pembrolizumab + Chemotherapy vs Part 2: Placebo + Chemotherapy; p = 0.0016; Hazard Ratio (HR) 0.75 (95% CI 0.62 to 0.91); Log Rank; NCT02819518 ↗
registry analysis (superiority test); Part 2: Pembrolizumab + Chemotherapy vs Part 2: Placebo + Chemotherapy; p = 0.0018; Hazard Ratio (HR) 0.66 (95% CI 0.50 to 0.88); Log Rank; NCT02819518 ↗
registry analysis (superiority test); Part 2: Pembrolizumab + Chemotherapy vs Part 2: Placebo + Chemotherapy; p = 0.0797; Hazard Ratio (HR) 0.89 (95% CI 0.76 to 1.05); Log Rank; NCT02819518 ↗
registry analysis (superiority test); Part 2: Pembrolizumab + Chemotherapy vs Part 2: Placebo + Chemotherapy; p = 0.0563; Hazard Ratio (HR) 0.86 (95% CI 0.72 to 1.04); Log Rank; NCT02819518 ↗
registry analysis (superiority test); Part 2: Pembrolizumab + Chemotherapy vs Part 2: Placebo + Chemotherapy; p = 0.0093; Hazard Ratio (HR) 0.73 (95% CI 0.55 to 0.95); Log Rank; NCT02819518 ↗
Publications
- Rugo HS, Cescon DW, Schmid P, Nowecki Z, Im SA, Md Yusof M, Gallardo C, Iwata H, Lipatov O, Cruz F, Barrios CH, Hegg R, Loi S, Gion M, Otero MT, Arkosy P, Tarnawski R, Yao L, Mejia J, Pan W, Cortes J. Outcomes in KEYNOTE-355 after chemotherapy discontinuation before pembrolizumab discontinuation and with immune-mediated adverse events. NPJ Breast Cancer. 2026 Jun 26. doi: 10.1038/s41523-026-00971-8. Online ahead of print.
- Im SA, Cortes J, Cescon DW, Yusof MM, Iwata H, Masuda N, Takano T, Huang CS, Chung CF, Tsugawa K, Park YH, Matsumoto K, Inoue K, Kwong A, Loi S, Fu W, Pan W, Karantza V, Rugo HS, Schmid P. Results from the randomized KEYNOTE-355 study of pembrolizumab plus chemotherapy for Asian patients with advanced TNBC. NPJ Breast Cancer. 2024 Sep 12;10(1):79. doi: 10.1038/s41523-024-00679-7.
- Cortes J, Rugo HS, Cescon DW, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Perez-Garcia J, Iwata H, Masuda N, Torregroza Otero M, Gokmen E, Loi S, Guo Z, Zhou X, Karantza V, Pan W, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2022 Jul 21;387(3):217-226. doi: 10.1056/NEJMoa2202809.
- Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Holgado E, Iwata H, Masuda N, Otero MT, Gokmen E, Loi S, Guo Z, Zhao J, Aktan G, Karantza V, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020 Dec 5;396(10265):1817-1828. doi: 10.1016/S0140-6736(20)32531-9.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Pembrolizumab | Monoclonal antibody | 200 mg | Intravenous |
| Background | Carboplatin | Small molecule | 2 unknown | Intravenous |
| Background | Gemcitabine | Small molecule | 1000 mg/m2 | Intravenous |
| Background | Nab-paclitaxel | Small molecule | 100 mg/m2 | Intravenous |
| Background | Paclitaxel | Small molecule | 90 mg/m2 | Intravenous |