Abstract 639TiP
Background
Neuroendocrine prostate cancer is an aggressive disease that can occur de novo or from previously treated metastatic castration-resistant prostate cancer (mCRPC). Based on histologic similarity to small cell lung cancer, the treatment for t-NE often includes platinum-containing chemotherapy, but there is no standard of care. The PD-1 inhibitor pembrolizumab has shown promising efficacy with acceptable safety in combination with olaparib, docetaxel, or enzalutamide for treatment of mCRPC in the multicohort phase Ib/II KEYNOTE-365 study (NCT02861573). In cohort I, platinum-containing chemotherapy alone or with pembrolizumab will be evaluated for pts with t-NE.
Trial design
Eligibility includes t-NE (≥1% neuroendocrine cells in a recent biopsy specimen confirmed by central histology review), progression within 6 months of screening, ECOG PS 0 or 1, and previously having received docetaxel for mCRPC. Pts may have previously received treatment with ≤2 NHAs for metastatic hormone-sensitive prostate cancer (mHSPC) or mCRPC and 1 other chemotherapy for mCRPC. Pts must also have had disease progression within 6 months of starting an NHA (mHSPC or mCRPC) and within <6 cycles of docetaxel for mCRPC. Pts will be randomly assigned 1:1 to receive pembrolizumab 200 mg IV on day 1 of each cycle Q3W + carboplatin AUC of 5 IV on day 1 + etoposide 100 mg/m2 IV on days 1, 2, and 3 of each 21-day cycle for 4 cycles in arm 1 or the same chemotherapy without pembrolizumab in arm 2. Treatment with pembrolizumab will continue up to 2 years, until disease progression, unacceptable toxicity, or withdrawal of consent. Pts will be stratified by ECOG PS status (0 vs 1). Each arm will have 40-100 pts. CT/MRI will be performed Q9W through week 54 and Q12W thereafter. Primary end points are safety and tolerability, PSA response rate, and ORR per RECIST v1.1 by blinded independent central review (BICR). Secondary end points are time to PSA progression, DOR and DCR per RECIST v1.1 by BICR; ORR, DOR, DCR, and rPFS per PCWG3-modified RECIST v1.1 by BICR; and OS. End points will be summarized for each arm without formal hypothesis testing.
Clinical trial identification
NCT02861573, August 10, 2016.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD of ApotheCom (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
N.D. Shore: Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Aurora Oncology; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Boston Scientific; Financial Interests, Personal, Advisory Role: Clovis Genesys; Financial Interests, Personal, Advisory Role: Dendreon; Financial Interests, Personal, Advisory Role: Exact Imaging; Financial Interests, Personal, Advisory Role: Exact Sciences; Financial Interests, Personal, Advisory Role: FerGene; Financial Interests, Personal, Advisory Role: Foundation Medicine; Financial Interests, Personal, Advisory Role: GenesisCare; Financial Interests, Personal, Advisory Role: Invitae; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: MDxhealth; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Myovant; Financial Interests, Personal, Advisory Role: Myriad; Financial Interests, Personal, Advisory Role: Nymox; Financial Interests, Personal, Advisory Role: Pacific Edge; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Phosphorous; Financial Interests, Personal, Advisory Role: PreView Medical; Financial Interests, Personal, Advisory Role: Propella; Financial Interests, Personal, Advisory Role: Sanofi Genzyme; Financial Interests, Personal, Advisory Role: Sensen Bio; Financial Interests, Personal, Advisory Role: Specialty Network; Financial Interests, Personal, Advisory Role: Tolmar; Financial Interests, Personal, Advisory Role: Urogen; Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Clovis Oncology; Financial Interests, Personal, Speaker’s Bureau: Foundation Medicine; Financial Interests, Personal, Speaker’s Bureau: Guardant; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: Myovant; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Tolmar. G. Kramer: Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Sanofi Genzyme; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Institutional, Funding: Bayer. A.M. Joshua: Financial Interests, Personal, Other, Honoraria: Merck. X.T. Li: Financial Interests, Personal, Full or part-time Employment: MSD. C.H. Poehlein: Financial Interests, Personal, Full or part-time Employment: Merck & Co.; Financial Interests, Personal, Stocks/Shares: Merck & Co. C. Schloss: Financial Interests, Personal, Full or part-time Employment: Merck & Co.; Financial Interests, Personal, Stocks/Shares: Merck & Co. J.S. de Bono: Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Amgen; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Astellas; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: AstraZeneca; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Bayer; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Bioxcel Therapeutics; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Cellcentric; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Daiichi; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Eisai; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Genentech Roche; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Genmab; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: GlaxoSmithKline; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Harpoon; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Janssen; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Menarini Silicon Biosystems; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Merck Serono; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Merck Sharp & Dohme; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Orion Pharma; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Pfizer; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Qiagen; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Sanofi Aventis; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Sierra Oncology; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Taiho; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Terumo; Financial Interests, Personal, Other, Honoraria, advisory/consultancy, travel expenses: Vertex Pharmaceuticals; Financial Interests, Institutional, Research Grant, Research grant/funding: Astellas; Financial Interests, Institutional, Research Grant, Research grant/funding: AstraZeneca; Financial Interests, Institutional, Research Grant, Research grant/funding: Bayer; Financial Interests, Institutional, Research Grant, Research grant/funding: Cellcentric; Financial Interests, Institutional, Research Grant, Research grant/funding: Daiichi; Financial Interests, Institutional, Research Grant, Research grant/funding: Genentech Roche; Financial Interests, Institutional, Research Grant, Research grant/funding: Genmab; Financial Interests, Institutional, Research Grant, Research grant/funding: GlaxoSmithKline; Financial Interests, Institutional, Research Grant, Research grant/funding: Harpoon; Financial Interests, Institutional, Research Grant, Research grant/funding: Janssen; Financial Interests, Institutional, Research Grant, Research grant/funding: Merck Serono; Financial Interests, Institutional, Research Grant, Research grant/funding: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant, Research grant/funding: Orion Pharma; Financial Interests, Institutional, Research Grant, Research grant/funding: Pfizer; Financial Interests, Institutional, Research Grant, Research grant/funding: Sanofi Aventis; Financial Interests, Institutional, Research Grant, Research grant/funding: Sierra Oncology; Financial Interests, Institutional, Research Grant, Research grant/funding: Taiho; Financial Interests, Institutional, Research Grant, Research grant/funding: Vertex Pharmaceuticals; Non-Financial Interests, Personal, Other, Licensing/Royaties: Patent WO 2005 053662; Non-Financial Interests, Personal, Other, Licensing/Royaties: Patent US5604213. E. Yu: Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Myovant Sciences; Financial Interests, Institutional, Research Grant: Dendreon; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Pharmacyclics; Financial Interests, Institutional, Research Grant: Blue Earth Diagnostics; Financial Interests, Institutional, Research Grant: Bayer.