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
1541 - TERT gene fusions characterize a subset of metastatic Leydig cell tumors
Presenter: Bozo Kruslin
Session: Poster Display session 3
Resources:
Abstract
5389 - Two-weekly accelerated BEP (aBEP) regimen as induction chemotherapy (CT) in intermediate and poor prognosis patients (pts) with nonseminomatous germ cell tumors (NSGCT): final results of phase II trial.
Presenter: Alexey Tryakin
Session: Poster Display session 3
Resources:
Abstract
2934 - Differential expression of circulating miR375 and miR371 to detect teratoma and viable germ cell malignancy
Presenter: Lucia Nappi
Session: Poster Display session 3
Resources:
Abstract
3585 - Prognosis of anaemia in disseminated testicular germ cell tumours. On behalf of the Spanish Germ Cell Cancer Group (SGCCG)
Presenter: Esmeralda Garcia Torralba
Session: Poster Display session 3
Resources:
Abstract
2254 - The Effects Of Primary Testicular Tumor Localization On Prognosis In Patients With Nonseminomatous Testis Cancer
Presenter: Birol Yildiz
Session: Poster Display session 3
Resources:
Abstract
4505 - Initial Results of a Phase II study of Nivolumab and Ipilimumab in Metastatic Adrenal Tumors.
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
3369 - NEMIO: a randomized phase II trial evaluating efficacy and safety of dose dense MVAC (ddMVAC) + durvalumab +/- tremelimumab as neoadjuvant treatment in patients with bladder muscle-invasive urothelial carcinoma
Presenter: Constance Thibault
Session: Poster Display session 3
Resources:
Abstract
4824 - KEYNOTE-905: A Phase 3 Study of Cystectomy Plus Perioperative Pembrolizumab Versus Cystectomy Alone in Cisplatin (cis)-Ineligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Matthew Galsky
Session: Poster Display session 3
Resources:
Abstract
2253 - Phase 3 LEAP-011 trial: First-Line Pembrolizumab With Lenvatinib in Patients With Advanced Urothelial Carcinoma Ineligible to Receive Platinum-Based Chemotherapy
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
4310 - PULSE : A Single Arm Trial Assessing The Activity and Safety of Avelumab Immunotherapy Maintenance among Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma (mSCPC).
Presenter: Noemie Gassian
Session: Poster Display session 3
Resources:
Abstract