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
3128 - Systemic bevacizumab for the treatment of recurrent respiratory papillomatosis: A retrospective analysis from an academic tertiary care center
Presenter: Sumita Trivedi
Session: Poster Display session 3
Resources:
Abstract
1242 - Monalizumab in combination with cetuximab in patients (pts) with recurrent or metastatic (R/M) head and neck cancer (SCCHN) previously treated or not with PD-(L)1 inhibitors (IO): 1-year survival data.
Presenter: Roger Cohen
Session: Poster Display session 3
Resources:
Abstract
4703 - Updated results of a phase II study evaluating accelerator-based boron neutron capture therapy (AB-BNCT) with borofalan(10B) (SPM-011) in recurrent squamous cell carcinoma (R-SCC-HN) and recurrent and locally advanced non-SCC (R/LA-nSCC-HN) of the head and neck
Presenter: Katsumi Hirose
Session: Poster Display session 3
Resources:
Abstract
3638 - Phase 3 KEYNOTE-048 Study of First-Line (1L) Pembrolizumab (P) for Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC): Asia vs Non-Asia Subgroup (subgrp) Analysis
Presenter: Makoto Tahara
Session: Poster Display session 3
Resources:
Abstract
2954 - Integrated data review evaluating safety, pharmacokinetics (PK) and immunogenicity of RM-1929 photoimmunotherapy (PIT) in subjects with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC).
Presenter: Jennifer Johnson
Session: Poster Display session 3
Resources:
Abstract
3629 - First line versus second line immunotherapy in recurrent/metastatic squamous cell carcinoma of the head and neck
Presenter: Caroline Even
Session: Poster Display session 3
Resources:
Abstract
767 - Sensitizing HRAS overexpressing head and neck squamous cell carcinoma (HNSCC) to chemotherapy
Presenter: Theodoros Rampias
Session: Poster Display session 3
Resources:
Abstract
4985 - A Single-Arm, Open-Label, Multicenter, Phase IIIb Clinical Trial with Nivolumab in Subjects with Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck.
Presenter: Paolo Bossi
Session: Poster Display session 3
Resources:
Abstract
1564 - Long-term Results of Phase 2 Trial of Reduced Modified Clinical Target Volume in Low-risk Nasopharyngeal Carcinoma Treated with Intensity Modulated Radiotherapy
Presenter: Jingjing Miao
Session: Poster Display session 3
Resources:
Abstract
3356 - To compare two oral mucosa contouring methods in predicting acute oral mucocitis in nasopharyngeal carcinoma treated with helical tomotherapy
Presenter: Yuan-Yuan Chen
Session: Poster Display session 3
Resources:
Abstract