Abstract 4824
Background
Current standard of care for pts with MIBC who are ineligible for neoadjuvant cis-based chemotherapy is radical cystectomy (RC) + pelvic lymph node dissection (PLND). Due to high rates of recurrence and relatively poor overall survival (OS) with RC + PLND alone, there is an urgent need for novel perioperative systemic therapy regimens. A recent single-arm study (PURE-01; NCT02736266) showed clinical activity of pembrolizumab as single-agent neoadjuvant therapy in pts with MIBC and that high PD-L1 expression was associated with a higher pathologic complete response rate.
Trial design
KEYNOTE-905 (NCT03924895) is a randomized, global, multicenter, phase 3 trial of perioperative pembrolizumab plus RC versus RC alone in cis-ineligible pts with MIBC. Approximately 610 adult (≥18 years) pts with histologically confirmed diagnosis of MIBC (T2-T4aN0M0) with predominant (≥50%) urothelial histology are eligible. Pts must be ineligible to receive cis, have an ECOG PS score of 0-2, and must not have previously received any systemic anticancer therapies for MIBC. Pts will be stratified by clinical T stage (T2 vs T3/4), PD-L1 combined positive score (CPS) (≥10 vs < 10), and geographic region. Pts will be randomly assigned 1:1 to receive either 3 cycles of neoadjuvant pembrolizumab followed by RC + PLND and then 14 cycles of adjuvant pembrolizumab or RC + PLND alone. Pembrolizumab 200 mg will be administered every 3 weeks. CT/MRI imaging will be performed before and after cystectomy. Pts who are disease-free at postcystectomy imaging will continue with serial imaging until progression/discontinuation; all imaging will be assessed by blinded independent central review. Coprimary end points are pathologic complete response (pT0N0) and event-free survival evaluated in pts whose tumors express PD-L1 CPS ≥10 and in all pts irrespective of CPS score. Secondary end points are OS, disease-free survival, and pathologic downstaging. Adverse events (AEs) will be monitored from randomization through 30 days after last dose of study drug (90 days for serious AEs). Patient-reported outcomes will also be measured.
Clinical trial identification
NCT03924895, April 23, 2019.
Editorial acknowledgement
Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA), 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
M. Galsky: Advisory / Consultancy: Janssen, Merck, Astellas, Genentech, BMS, Novartis, Pfizer, EMD Serono, AstraZeneca, Seattle Genetics, Incyte, Aileron, Dracen, Ionvio, NuMab, Dragonfly Therapeutics; Research grant / Funding (institution): Dendreon, Novartis, BMS, Merck, AstraZeneca, Genentech/Roche. A. Necchi: Honoraria (self): Merck, Roche, AstraZeneca, Janssen, Rainier Therapeutics, Bayer, BMS, Clovis; Advisory / Consultancy: Merck, Roche, AstraZeneca, Janssen, Rainier Therapeutics, Bayer, BMS, Clovis; Research grant / Funding (institution): Merck, AstraZeneca; Spouse / Financial dependant: Bayer. N.D. Shore: Advisory / Consultancy: Amgen, Astellas, AstraZeneca, Bayer, BMS, Dendreon, Ferring, Janssen, Merck, MDxHealth, Pfizer, Sanofi, Tolmar; Speaker Bureau / Expert testimony: Astellas, Janssen. F. Witjes: Advisory / Consultancy: Roche, MSD, BMS. K. Nam: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. J.L. Godwin: Full / Part-time employment: Merck & Co., Inc. T.L. Frenkl: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: MSD. E.R. Plimack: Advisory / Consultancy: BMS, Genentech, Incyte, Janssen, Merck; Research grant / Funding (institution): Astellas, BMS, Genentech, Merck, Peloton, Pfizer.
Resources from the same session
5529 - Safety and efficacy of Ac-225-PSMA-617 in metastatic castration resistant prostate cancer (mCRPC) after failure of Lu-177-PSMA
Presenter: Robert Tauber
Session: Poster Display session 3
Resources:
Abstract
3611 - Phase II trial of SM 88 in Non-Metastatic Biochemical Recurrent Prostate Cancer.
Presenter: Benjamin Gartrell
Session: Poster Display session 3
Resources:
Abstract
2492 - A phase 1 study of Ad5 PSA/MUC-1/Brachyury Vaccine in Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC)
Presenter: Marijo Bilusic
Session: Poster Display session 3
Resources:
Abstract
3142 - Multicenter Phase I Trial of a DNA Vaccine Encoding the Androgen Receptor Ligand Binding Domain (pTVG-AR, MVI-118) in Patients with Metastatic Prostate Cancer
Presenter: Douglas McNeel
Session: Poster Display session 3
Resources:
Abstract
4327 - Impact of germline mutations in Homologous Recombination (HR) genes on the response to Radium-223 for metastatic castration resistant prostate cancer (mCRPC)
Presenter: Elena Castro
Session: Poster Display session 3
Resources:
Abstract
3600 - Serum biomarkers of bone metabolism in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with Radium-223 (Ra223): Results from a prospective multicentre study
Presenter: Nuria Romero Laorden
Session: Poster Display session 3
Resources:
Abstract
3742 - Prognostic value of tumor suppression genes (TP53, PTEN, Rb) in metastatic hormone sensitive prostate cancer
Presenter: Miguel Gonzalez Velez
Session: Poster Display session 3
Resources:
Abstract
2643 - Germline sequencing of advanced prostate cancer patients in the BARCODE2 trial
Presenter: Sarah Benafif
Session: Poster Display session 3
Resources:
Abstract
4349 - Impact of treatment sequence in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): data from the prospective PROREPAIR-B study.
Presenter: Carlo Cattrini
Session: Poster Display session 3
Resources:
Abstract
3301 - Implications of Single Nucleotide Polymorphisms (SNPs) in Androgen Related-Genes in Outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with Abiraterone (Abi) and Enzalutamide (Enza)
Presenter: Isabel Aragon
Session: Poster Display session 3
Resources:
Abstract