Abstract 2075
Background
MIBC is associated with a high rate of recurrence and poor overall prognosis despite aggressive local and systemic therapy. With standard therapy of neoadjuvant cis-based chemotherapy (CT), only a modest 5-year survival benefit is seen after radical cystectomy (RC). Recently, neoadjuvant CT and pembro showed efficacy in cis-eligible pts with MIBC (NCT02365766).
Trial design
KEYNOTE-866 (NCT03924856) is a randomized, multicenter, global, phase 3 trial to assess efficacy and safety of perioperative pembro + CT vs perioperative pbo + CT for pts with MIBC. Adult pts (≥18 y) with histologically confirmed MIBC (T2-T4aN0M0) with predominant (≥50%) urothelial histology, confirmed by blinded independent central review, are eligible. Pts must be previously untreated, be cis-eligible, have ECOG PS 0/1, and have tumor tissue for histology and PD-L1 analysis. About 790 pts will be randomly assigned 1:1 to receive 4 cycles of neoadjuvant pembro + CT followed by 13 cycles of adjuvant pembro after RC + pelvic lymph node dissection (PLND) or 4 cycles of neoadjuvant pbo + CT followed by 13 cycles of adjuvant pbo after RC + PLND. Neoadjuvant/adjuvant pembro 200 mg will be administered every 3 weeks (Q3W); neoadjuvant CT consists of 4 cycles of gemcitabine 1000 mg/m2 + cis 70 mg/m2 Q3W. Pts will be stratified by PD-L1 status (combined positive score [CPS] ≥10 vs < 10), disease stage (T2 vs T3/4) and region (USA vs EU vs most of world). CT/MRI will be performed ≤5 wk pre-cystectomy, 6 wk post-cystectomy, and Q12W up to 96 wk post-cystectomy imaging, and at discontinuation; then, Q24W in year 3 and beyond. Primary end points are pathologic complete response (pCR) and event-free survival (EFS) 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 in populations described for pCR and EFS, as well as safety, and patient-reported outcomes. Adverse events (AEs; graded per NCI CTCAE v4.0) will be monitored from randomization through 30 days after last dose of study drug (90 days for serious AEs).
Clinical trial identification
NCT03924856, 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
A.O. Siefker-Radtke: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar Therapeutics; Advisory / Consultancy, Travel / Accommodation / Expenses: Seattle Genetics; Advisory / Consultancy: Bavarian Nordic. G. Steinberg: Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Shareholder / Stockholder / Stock options: Urogen; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Boston Scientific; Honoraria (self), Advisory / Consultancy: Cold Genesys; Honoraria (self), Advisory / Consultancy: PhotoCure; Honoraria (self), Advisory / Consultancy: Aduro; Honoraria (self), Advisory / Consultancy: Asieris; Honoraria (self), Advisory / Consultancy: Ciclomed; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: MDxHealth; Honoraria (self), Advisory / Consultancy: Ferring; Honoraria (self), Advisory / Consultancy: Fidia; Shareholder / Stockholder / Stock options: Epivax Oncology. J. Bedke: Advisory / Consultancy: BMS, Roche, MSD, Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS, Roche, MSD. J. Martin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. R. Kataria: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. T.L. Frenkl: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: MSD. C.J. Hoimes: Advisory / Consultancy: Seattle Genetics, Merck; Speaker Bureau / Expert testimony: Bristol-Myers Squibb, Genentech. All other authors have declared no conflicts of interest.
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