2237 - KEYNOTE-921: phase 3 study of pembrolizumab (pembro) plus docetaxel and prednisone for enzalutamide (enza)- or abiraterone (abi)-pretreated patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

Background

Docetaxel is an established treatment for pts with mCRPC. Docetaxel plus the programmed death 1 (PD-1) inhibitor pembro and prednisone had activity in patients treated with abi or enza for mCRPC in the phase 1b/2 KEYNOTE-365 study (NCT02861573). KEYNOTE-921 (NCT03834506) is a randomized phase 3 trial to evaluate efficacy and safety of pembro plus docetaxel and prednisone in chemotherapy-naive pts who were previously treated with enza- or abi for mCRPC and had progression while on therapy.

Trial design

Adult (≥18 y) pts with chemotherapy-naive histologically or cytologically confirmed mCRPC who had progression while on androgen deprivation therapy (or postbilateral orchiectomy) within 6 months before screening were eligible. Pts must have had progression after ≥8 wk (≥14 wk for those with bone progression) or become intolerant after ≥4 wk of abi or enza treatment (but not both) with androgen-deprivation therapy in the chemotherapy-naive mCRPC state. Pts must have ECOG PS 0/1, adequate organ function, and tissue for biomarker analysis. Pts will be randomly assigned 1:1 to receive docetaxel 75 mg/m² every 3 wks (Q3W) plus prednisone/prednisolone 5 mg twice daily (BID) and pembro 200 mg Q3W or docetaxel 75 mg/m² Q3W plus prednisone/prednisolone 5 mg BID plus placebo Q3W. Treatment will be stratified per prior next-generation hormonal agent treatment (abi/enza) and metastases (bone only/liver/other). Responses will be assessed by CT/MRI and radionuclide bone imaging per PCWG3-modified RECIST v1.1 by blinded independent central review Q9W during the first year and Q12W thereafter. Treatment will continue with docetaxel and prednisone for up to 10 cycles and with pembro for up to 35 cycles or until radiographic disease progression, unacceptable toxicity, or consent withdrawal. Primary end points: overall survival and radiographic progression-free survival. The key secondary efficacy end point is time to initiation of subsequent anticancer therapy or death; safety and tolerability will also be reported. Approximately 1000 pts will be enrolled.

Clinical trial identification

NCT03834506; February 8, 2019.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

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, Research grant / Funding (institution): Ada Cap (Advanced Accelerator Applications); Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Clovis; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy: Exelixis; Research grant / Funding (institution): Endocyte; Advisory / Consultancy: Incyte; Research grant / Funding (institution): Innocrin; Advisory / Consultancy: Incyte; Research grant / Funding (institution): Genentech; Advisory / Consultancy: Janssen, Pharmacyclics, Urogen; Research grant / Funding (institution): MedImmune, Merck; Research grant / Funding (institution): Novartis, Progenics, Sanofi Aventis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer, Roche Laboratories, Seattle Genetics; Shareholder / Stockholder / Stock options: Bellicum, Tyme. B. Li: Full / Part-time employment: Merck & Co., Inc. C. Schloss: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. K. Fizazi: Advisory / Consultancy: Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Astellas; Advisory / Consultancy: Orion; Advisory / Consultancy: MSD; Advisory / Consultancy: Bayer.