234TiP - KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (PBO) + chemo for previously unt...

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cytotoxic agents
Breast Cancer
Biological therapy
Presenter Javier Cortes Castan
Citation Annals of Oncology (2017) 28 (suppl_5): v68-v73. 10.1093/annonc/mdx364
Authors J. Cortes Castan1, Z. Guo2, V. Karantza2, G. Aktan3
  • 1Oncology, Ramon y Cajal Hospital, 08035 - Madrid/ES
  • 2Oncology, Merck & Co., Inc., Kenilworth/US
  • 3Clinical Research, Merck & Co., Inc., Kenilworth/US



In the phase Ib KEYNOTE-012 study, the anti–PD-1 antibody pembro demonstrated promising antitumor activity and acceptable safety as monotherapy in pretreated patients (pts) with PD-L1+ mTNBC. Adding pembro to chemo may enhance antitumor activity. KEYNOTE-355 (NCT02819518) is a global phase III study of pembro+chemo vs PBO+chemo in pts with previously untreated, locally recurrent, inoperable TNBC/mTNBC.

Trial design

Eligible pts are ≥18 y and have centrally confirmed, locally recurrent, inoperable TNBC or mTNBC not previously treated with chemo (prior chemo in [neo]adjuvant setting allowed); measurable disease per RECIST v1.1; ECOG PS 0-1; ≥6 mo between definitive surgery or last dose of adjuvant chemo, whichever was last; and first disease recurrence (≥12 mo if prior treatment with same-class agent). Part 1 is an open-label, unblinded safety run-in of ∼30 pts distributed over 3 arms (pembro+nab-paclitaxel, pembro+paclitaxel, pembro+gemcitabine/carboplatin). Part 2 is a double-blind, PBO-controlled study of ∼828 pts to be randomized 2:1 to pembro 200 mg every 3 weeks + chemo (nab-paclitaxel 100 mg/m2 on d 1, 8, and 15 every 28 d; paclitaxel 90 mg/m2 on d 1, 8, and 15 every 28 d; or gemcitabine 1000 mg/m2 + carboplatin AUC 2 on d 1 and 8 every 21 d) or PBO+chemo. Crossover not allowed. Stratification factors are study chemo (taxane vs gemcitabine/carboplatin), tumor PD-L1 expression (+/-), and prior therapy with same-class agent in the (neo)adjuvant setting (yes/no). Treatment will occur for ≤35 administrations (pembro/PBO only) or until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or decision to discontinue. Primary end points are safety in part 1 and PFS (by RECIST v1.1, central radiology review) and OS in part 2; secondary end points include ORR (by RECIST v1.1, central radiology review), duration of response. AEs will be graded per NCI CTCAE v4.0. Response will be assessed at wks 8, 16, 24, then at 9-wk intervals up to 1 y, and at 12-wk intervals thereafter. Interim safety analysis will occur after pts complete 1 treatment cycle in part 1.

Clinical trial identification

EUDRACT number: 2016-001432-35 ClinicalTrials.gov, NCT02819518

Legal entity responsible for the study

Merck & Co., Inc., Kenilworth, NJ, USA


Merck & Co., Inc., Kenilworth, NJ, USA


J. Cortes Castan: Advisory board member for Roche, Celgene, Aztrazeneca, Cellestia Biotech, Biothera. Honoraria from Roche, Novartis, Eisai, Celgene, Pfizer. Z. Guo, V. Karantza, G. Aktan: Employment and stock ownership: Merck.