233TiP - Pembrolizumab (pembro) or placebo added to docetaxel and prednisone/prednisolone for metastatic castration-resistant prostate cancer (mCRPC) previously treated with next-generation hormonal agents (NHAs): KEYNOTE-921 phase III study

Background

Pembro is a humanized monoclonal antibody that binds to PD-1 and prevents interaction with its ligands, PD-L1 and PD-L2. In the KEYSTONE-365 phase Ib/II study (NCT02861573), pembro added to docetaxel + prednisone had antitumor activity for mCRPC after progression with abiraterone acetate/enzalutamide. The randomized, phase III KEYNOTE-921 study (NCT03834506) will be conducted to assess efficacy and safety of pembro vs placebo added to docetaxel + prednisone in patients with mCRPC whose disease progressed on NHAs and who have not received chemotherapy.

Trial design

Eligibility criteria include histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology; evidence of metastatic disease or PSA (PCWG3), soft tissue (RECIST v1.1), or bone (PCWG3) progression; prior treatment with 1 (but not more than 1) NHA (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) for metastatic hormone-sensitive prostate cancer or CRPC (nonmetastatic or metastatic); ongoing androgen deprivation; and Eastern Cooperative Oncology Group performance status 0 or 1. Key exclusion criteria were prior treatment with docetaxel/other chemotherapy, therapeutic radiopharmaceutical agents, or other systemic therapies. Approximately 1000 enrolled patients will be randomly assigned 1:1 to receive pembro 200 mg or placebo Q3W (≤35 cycles) added to docetaxel 75 mg/m² IV Q3W and prednisone 5 mg PO BID (≤10 cycles) until disease progression, unacceptable toxicity, or withdrawal. Response will be assessed using PCWG3-modified RECIST v1.1 by blinded independent central review (BICR) by imaging (CT/MRI/bone) Q9W through week 54 and then Q12W. The coprimary end points are OS and rPFS; additional details are in the table Table: 233TiP

End points in KEYNOTE-921

^aDecrease of ≥50% from baseline, measured twice ≥3 weeks apart.

Clinical trial identification

NCT03834506, February 8, 2019.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

D.P. Petrylak: Advisory/Consultancy: Ada Cap (Advanced Accelerator Applications) Amgen, Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly, Exelixis, Incyte, Janssen, Mirati, Monopteros, Pfizer, Pharmacyclics, Roche, Sea; Shareholder/Stockholder/Stock options, Sold 10/2019: Bellicum, Tyme; Research grant/Funding (institution), *Denotes study trials that have terminated: Ada Cap (Advanced Accelerator Applications), Agensys Inc, *Astellas, AstraZeneca, *Bayer, BioXcel Therapeutics, Bristol-Myers Squibb, Clovis Oncology, Eisai, *Eli Lilly, *Endocyte, Genentech, *Innocrin, MedImmune, Medivation, Merck, Mirati, *Novartis, Pfi. N.D. Shore: Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Dendreon, Ferring, Fergene, Janssen, Merck, MDxHealth, Myovant, Nymox, Pfizer, Sanofi-Genzyme, Tolmar; Speaker Bureau/Expert testimony: Bayer, Janssen, Pfizer, Astellas; Leadership role, Immediate Past President: LUGPA. R. Ratta: Advisory/Consultancy: Astellas. J.M. Piulats: Advisory/Consultancy: Roche, Novartis, Jansen, Astellas, Bayer, Sanofi-Genzyme, MSD, Bristol-Myers Squibb, Merk-Serono, Clovis, AstraZeneca, Beigene, VCN Biotech; Research grant/Funding (self): Roche, Jansen, Astellas, MSD, Bristol-Myers Squibb, Merk-Serono, AstraZeneca, Beigene, VCN Biotech; Travel/Accommodation/Expenses: Roche, Astellas, Jansen. B. Li: Full/Part-time employment: MSD R&D (China) Co., Ltd. C. Schloss: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. K. Fizazi: Advisory/Consultancy: Amgen, Janssen, Sanofi, Astellas, Orion, MSD, Bayer. All other authors have declared no conflicts of interest.