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
5763 - cfDNA is an acceptable but insufficient means of characterizing FGFR3 mutation in patients with metastatic urothelial cancer (mUC)
Presenter: Sumanta Pal
Session: Poster Display session 3
Resources:
Abstract
5877 - Efficacy of anti-PD(L)1 treatment in patients with metastatic urothelial cancer based on mRNA- and protein- based PD-L1 determination: Results from the multicentric, retrospective FOsMIC trial
Presenter: Jonas Jarczyk
Session: Poster Display session 3
Resources:
Abstract
5204 - A differential bladder microbiota composition is associated with tumor grade in bladder cancer.
Presenter: Monica Parra-Grande
Session: Poster Display session 3
Resources:
Abstract
4904 - Molecular characterization of metastatic urothelial carcinoma (mUC) in prior or current smokers (PCS) vs non-smokers (NS)
Presenter: Victor Sacristan Santos
Session: Poster Display session 3
Resources:
Abstract
5370 - Evaluation of different diagnostic methods for identification of FGFR alteration in advanced urothelial carcinomas: Proficiency Results based on multiple RNA extraction kits and mutation detection methods
Presenter: Veronika Weyerer
Session: Poster Display session 3
Resources:
Abstract
2579 - Title: Genomic characterization of non-schistosomiasis-related squamous cell carcinoma (NSR-SCC) of the urinary bladder: a retrospective study of potential prognostic and predictive biomarkers
Presenter: Esmail Al-ezzi
Session: Poster Display session 3
Resources:
Abstract
2203 - TiNivo: Tivozanib combined with nivolumab results in prolonged progression free survival in patients with metastatic renal cell carcinoma (mRCC). Final Results.
Presenter: Philippe Barthelemy
Session: Poster Display session 3
Resources:
Abstract
4712 - First-Line Pembrolizumab (pembro) Monotherapy for Advanced Non‒Clear Cell Renal Cell Carcinoma (nccRCC): Updated Follow-Up for KEYNOTE-427 Cohort B
Presenter: Cristina Suárez
Session: Poster Display session 3
Resources:
Abstract
2091 - First-Line Pembrolizumab (pembro) Monotherapy in Advanced Clear Cell Renal Cell Carcinoma (ccRCC): Updated Follow-Up For KEYNOTE-427 Cohort A
Presenter: James Larkin
Session: Poster Display session 3
Resources:
Abstract
2368 - Association Between Depth of Response and Overall Survival: Exploratory Analysis in Patients With Previously Untreated Advanced Renal Cell Carcinoma (aRCC) in CheckMate 214
Presenter: Viktor Grünwald
Session: Poster Display session 3
Resources:
Abstract