Abstract 2507
Background
In mCRPC pts unselected for homologous recombination deficiency (HRD), promising activity was seen with combination programmed death 1 inhibitor pembro and OLA in the phase 1b/2 KEYNOTE-365 study (NCT02861573), warranting further investigation in this population. KEYLYNK-010 (NCT03834519) is a phase 3, randomized, open-label trial to evaluate efficacy and safety of pembro plus OLA in molecularly unselected ENZA- or ABI-pretreated pts with mCRPC whose disease progressed with CTx.
Trial design
Eligible pts (≥18 years) must have histologically confirmed mCRPC and prior treatment (tx) with ABI or ENZA (but not both) and prior tx with CTx (1 prior docetaxel-based regimen). Pts must have an ECOG PS of 0/1, adequate organ function, and tumor tissue for biomarker analysis. Pts will be randomly assigned 2:1 to receive pembro 200 mg intravenously Q3W plus OLA 300 mg orally twice daily or ABI 1000 mg orally once daily plus prednisone/prednisolone 5 mg orally twice daily (for ENZA-pretreated pts) or ENZA 160 mg/day orally (for ABI-pretreated pts). Arms will be stratified per prior tx (ABI/ENZA) and presence of measurable disease (yes/no). Responses will be assessed by CT/MRI and radionuclide bone imaging per PCWG-modified RECIST v1.1 by blinded independent central review (BICR) Q9W during the first year and Q12W thereafter. Tx will continue with up to 2 years of pembro (35 cycles) and OLA or ABI/ENZA until radiographic disease progression, unacceptable toxicity, or consent withdrawal. Primary end points are overall survival and radiographic progression-free survival. The key secondary efficacy end point is time to initiation of subsequent anticancer therapy or death. Other secondary end points are objective response rate and duration of response per PCWG-modified RECIST v1.1 by BICR, time to first symptomatic skeletal event, and safety and tolerability. Prognostic or predictive molecular biomarkers (eg, genomic HRD status) will be explored. Approximately 780 pts will be enrolled.
Clinical trial identification
NCT03834519; February 8, 2019.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Matt Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was 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
E. Yu: Advisory / Consultancy: Merck, Bayer, Amgen, Pharmacyclics, Seattle Genetics; Research grant / Funding (self): Merck, Agensys, Dendreon, Seattle Genetics, Taiho, Daiichi-Sankyo; Travel / Accommodation / Expenses: Merck, Bayer, Amgen, Pharmacyclics, Seattle Genetics. J. Kim: Full / Part-time employment: Merck & Co., Inc.; Shareholder / Stockholder / Stock options: Merck & Co., Inc. E.S. Antonarakis: Honoraria (self), Research grant / Funding (self): Janssen, Sanofi, Dendreon, AstraZeneca, Clovis, Merck; Advisory / Consultancy: Astellas, Medivation, ESSA, Eli Lilly; Research grant / Funding (self): Johnson & Johnson, Genentech, Novartis, BMS; Non-remunerated activity/ies, Patent holder: Qiagen. All other authors have declared no conflicts of interest.
Resources from the same session
2600 - Atezolizumab (atezo) vs chemotherapy (chemo) in patients (pts) with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): a long-term overall survival (OS) and safety update from the Phase III IMvigor211 study
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3598 - Three-Year Follow-Up From the Phase 3 KEYNOTE-045 Trial: Pembrolizumab (Pembro) Versus Investigator’s Choice (Paclitaxel, Docetaxel, or Vinflunine) in Recurrent, Advanced Urothelial Cancer (UC)
Presenter: Andrea Necchi
Session: Poster Display session 3
Resources:
Abstract
2382 - First Report of Efficacy and Safety From a Phase 2 Trial of Tislelizumab, an Anti-PD-1 Antibody, for the Treatment of PD-L1+ Locally Advanced or Metastatic Urothelial Carcinoma (UC) in Asian Patients
Presenter: Dingwei Ye
Session: Poster Display session 3
Resources:
Abstract
2388 - Quality of Life of Metastatic Urothelial Cancer (mUC) Patients Treated with Enfortumab Vedotin (EV) Following Platinum-Containing Chemotherapy and a Checkpoint Inhibitor (CPI): Data from EV-201 Cohort 1
Presenter: Bradley McGregor
Session: Poster Display session 3
Resources:
Abstract
3748 - Safety and efficacy of atezolizumab (atezo) in patients (pts) with autoimmune disease (AID): subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
1126 - Validation of the VIO prognostic index in patients with metastatic urothelial carcinoma treated with immune-checkpoint inhibitors
Presenter: Rafael Morales Barrera
Session: Poster Display session 3
Resources:
Abstract
3693 - Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer
Presenter: Justin Matulay
Session: Poster Display session 3
Resources:
Abstract
4840 - Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
1221 - Clinical outcomes by sex with atezolizumab (atezo) monotherapy in patients (pts) with locally advanced/metastatic urothelial carcinoma (mUC)
Presenter: Jean Hoffman-censits
Session: Poster Display session 3
Resources:
Abstract
1715 - National Small Cell Bladder Cancer Audit: Results from 26 UK institutions
Presenter: Caroline Chau
Session: Poster Display session 3
Resources:
Abstract