89TiP - KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo for previously untreated, locally recurrent, inoperable or metastatic triple-negative breast cancer (mTNBC)

Abstract

Background: Pembro monotherapy demonstrated promising antitumor activity and acceptable safety in pretreated patients (pts) with PD-L1+ mTNBC in the phase Ib KEYNOTE-012 study. The addition of pembro to chemo may enhance antitumor activity. KEYNOTE-355 is a global phase III study comparing pembro + chemo to PBO + chemo in pts with locally recurrent, inoperable, and previously untreated TNBC/mTNBC. Trial design: Eligible pts are ≥18 y, have centrally confirmed, locally recurrent inoperable TNBC or mTNBC not treated previously with chemo (prior [neo]adjuvant chemo allowed); measurable disease per RECIST v1.1; ECOG PS 0-1; ≥6 mo between definitive breast 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 randomized 2:1 to pembro 200 mg Q3W + 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 is not allowed. Stratification factors are study chemo (taxane vs gemcitabine/carboplatin), prior therapy with same-class agent in (neo)adjuvant setting (yes/no), and tumor PD-L1 expression (+/-). Treatment will occur for ≤35 administrations (pembro/PBO only) or until confirmed disease progression, unacceptable toxicity, decision to discontinue, or withdrawal of consent. 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) and duration of response. AEs will be graded per NCI CTCAE v4.0. Responses will be assessed at wk 8, 16, 24, then at 9-wk intervals up to 1 y, and 12-wk intervals thereafter. An interim safety analysis will occur in part 1 after pts complete 1 treatment cycle. Clinical trial indentification: NCT02819518. Legal entity responsible for the study: Merck & Co., Inc., Kenilworth, NJ, USA Funding: Merck & Co., Inc., Kenilworth, NJ, USA Disclosure: J. Cortes Castan: Advisory board: Roche, Celgene, AztraZeneca, Cellestia Biotech, and Biothera Honoraria: Roche, Novartis, Eisai, Celgene, Pfizer, Z. Guo, V. Karantza: Employment and stock ownership: Merck & Co., Inc. G. Aktan: Employment and stock ownership: Merck & Co., Inc. Travel expenses: Merck & Co., Inc.