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
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
2075 - KEYNOTE-866: Phase 3 Study of Perioperative Pembrolizumab (pembro) or Placebo (pbo) in Combination With Neoadjuvant Chemotherapy in Cisplatin (cis)-Eligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Arlene Siefker-Radtke
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