Abstract 3140
Background
Poly(ADP-ribose) polymerases (PARPs) play a key role in DNA damage repair (DDR). DDR defects due to HRRm (eg BRCA mutation [BRCAm]) or resulting in HRD (eg global loss of heterozygosity) may sensitize tumors to PARP inhibitors, eg olaparib. Olaparib monotherapy has activity in BRCAm ovarian, breast, pancreatic, and prostate cancer, and in prostate cancer with DDR defects beyond BRCAm (TOPARP). Olaparib improved efficacy outcomes vs placebo/chemotherapy as treatment in ≤ 3rd-line (3L) HER2-negative BRCAm breast cancer (OlympiAD) and ≥2L BRCAm ovarian cancer (SOLO3), and maintenance therapy in ≥ 1L ovarian cancer irrespective of BRCAm (SOLO1, Study 19). LYNK-002 (NCT03742895) evaluates HRRm/HRD positivity (HRD+; per Lynparza HRR-HRD assay, Foundation Medicine, Inc., Cambridge, MA) as biomarkers of tumor-agnostic response to olaparib.
Trial design
This open-label, phase 2 study will enroll ∼370 patients (pts) ≥18 y with previously treated, histologically/cytologically confirmed HRRm/HRD + (per Lynparza HRR-HRD assay) advanced solid tumors who failed/are intolerant to/ineligible for available SOC and have no PD during prior platinum-based treatment (any number of prior regimens), measurable disease per RECIST v1.1/Prostate Cancer Working Group (PCWG)-modified RECIST v1.1, no CNS metastases, ECOG PS 0–1, and no persistent toxicity from prior therapy. Newly obtained/archival tumor samples will be centrally evaluated using the Lynparza HRR-HRD assay to confirm eligibility. Pts will be grouped into 2 cohorts: 1) solid tumors with BRCAm (n∼84; excluding breast and ovarian), 2) solid tumors with HRRm (BRCA non-mutated; n∼174)/HRD (n∼112) per Lynparza HRR-HRD assay. Pts will receive olaparib 300 mg BID until documented PD/unacceptable toxicity/study withdrawal. Tumor imaging will occur at baseline, Q8W for 1 y, and then Q12W per RECIST v1.1 by BICR/PCWG-modified RECIST v1.1 (modified for ≤5 target lesions/organ; 10 total). Primary endpoint is ORR. Key secondary endpoints are DOR, PFS, and OS. AEs will be graded using NCI CTCAE v4.0. Enrollment is ongoing at 51 sites in 15 countries. As of Apr 18, 2019, 23 patients have been enrolled.
Clinical trial identification
NCT03742895.
Editorial acknowledgement
Cindy Taylor, PhD, of C4 MedSolutions, LLC (Yardley, PA, USA), a CHC Group company, funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and AstraZeneca.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and AstraZeneca.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and AstraZeneca.
Disclosure
D. Hyman: Travel / Accommodation / Expenses, Personal fees: Atara Biotherapeutics; Travel / Accommodation / Expenses, Personal fees: Chugai Pharma; Travel / Accommodation / Expenses, Personal fees: CytomX Therapeutics; Travel / Accommodation / Expenses, Personal fees: Boehringer Ingelheim; Travel / Accommodation / Expenses, Personal fees: AstraZeneca; Research grant / Funding (institution), Research funding: Puma Biotechnology; Research grant / Funding (institution), Research funding: AstraZeneca; Research grant / Funding (institution), Research funding: Loxo Oncology. A. Hendifar: Advisory / Consultancy: Novartis; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Perthera. H. Cheol Chung: Research grant / Funding (institution): Lilly; Research grant / Funding (institution): GSK; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Merck-Serono; Research grant / Funding (institution): BMS/Ono; Research grant / Funding (institution): Taiho; Honoraria (institution): Merck-Sorono; Honoraria (institution): Lilly/Foundation Medicine; Advisory / Consultancy: Taiho; Advisory / Consultancy: Celltrion; Advisory / Consultancy: MSD; Advisory / Consultancy: Lilly; Advisory / Consultancy: Quintiles; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck-Serono. M. Maio: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Incyte; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Glaxo SmithKline; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Roche. A. Leary: Advisory / Consultancy, Advisory board: Tesaro; Advisory / Consultancy, Advisory board: AstraZeneca; Advisory / Consultancy, Advisory board: Clovis; Advisory / Consultancy, Advisory board: GamaMabs; Advisory / Consultancy, Advisory board: Gridstone; Advisory / Consultancy, Advisory board: Seattle Genetics; Research grant / Funding (institution), Research funding from the lab: Merus; Research grant / Funding (institution), Research funding from the lab: Inivata; Research grant / Funding (institution), Research funding from the lab: GamaMabs. J. Rhee: Full / Part-time employment: AstraZeneca Pharmaceuticals LP. M. Marton: Full / Part-time employment: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. M. Chen: Full / Part-time employment: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. S. Krishnan: Full / Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. R. Shapira: Speaker Bureau / Expert testimony, Speaker honoraria: MSD; Speaker Bureau / Expert testimony, Speaker honoraria: BMS; Speaker Bureau / Expert testimony, Speaker honoraria: Roche; Speaker Bureau / Expert testimony, Speaker honoraria: Novartis; Speaker Bureau / Expert testimony, Speaker honoraria: AstraZeneca. All other authors have declared no conflicts of interest.
Resources from the same session
2507 - KEYLYNK-010: Phase 3 Study of Pembrolizumab (pembro) Plus Olaparib (OLA) vs Enzalutamide (ENZA) or Abiraterone (ABI) in ENZA- or ABI-Pretreated Patients (pts) With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Who Had Progression on Chemotherapy (CTx)
Presenter: Evan Yu
Session: Poster Display session 3
Resources:
Abstract
2944 - PROSTRATEGY: A Spanish Genitourinary Oncology Group (SOGUG) multi-arm multistage (MAMS) phase III trial of immunotherapy strategies in high-volume metastasic hormone-sensitive prostate cancer.
Presenter: Jose Arranz Arija
Session: Poster Display session 3
Resources:
Abstract
3535 - A phase 1 study of AMG 160, a half-life extended bispecific T cell engager (HLE BiTE) immuno-oncology therapy targeting PSMA, in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)
Presenter: Ben Tran
Session: Poster Display session 3
Resources:
Abstract
4951 - ProBio: An outcome-adaptive, multi-arm, open-label, multiple assignment randomised controlled biomarker-driven trial in patients with metastatic castration-resistant prostate cancer (EudraCT: 2018-002350-78, NCT03903835)
Presenter: Johan Lindberg
Session: Poster Display session 3
Resources:
Abstract
2892 - A phase 3 randomized, placebo-controlled, double-blind study of niraparib plus abiraterone acetate and prednisone versus abiraterone acetate and prednisone in patients with metastatic prostate cancer (NCT03748641)
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
2427 - The Extended/Phase II Study of Safety And Tolerability Of Proxalutamide (GT0918) In Subjects With Metastatic Castrate Resistant Prostate Cancer (mCRPC) Who Failed Either Abiraterone (Abi) Or Enzalutamide (Enza)
Presenter: Nicholas Vogelzang
Session: Poster Display session 3
Resources:
Abstract
3224 - Addition of an oral docetaxel treatment (ModraDoc006/r) to androgen deprivation therapy (ADT) and intensity-modulated radiation therapy (IMRT) in patients with high risk N+M0 prostate cancer
Presenter: Marit Vermunt
Session: Poster Display session 3
Resources:
Abstract
3312 - A phase II randomized, open-label study comparing salvage radiotherapy in combination with 6 months of androgen-deprivation therapy with LHRH agonist or antagonist versus anti-androgen therapy with apalutamide in patients with biochemical progression after radical prostatectomy.
Presenter: Piet Dirix
Session: Poster Display session 3
Resources:
Abstract
2829 - Health-Related Quality of Life (HRQoL) and Updated Follow-Up From KEYNOTE-057: Phase 2 Study of Pembrolizumab (pembro) for Patients (pts) With High-Risk (HR) Non–Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guérin (BCG)
Presenter: Ronald de Wit
Session: Poster Display session 3
Resources:
Abstract
2673 - Clinical activity of vofatamab (V), an FGFR3 selective antibody in combination with pembrolizumab (P) in metastatic urothelial carcinoma (mUC), updated interim analysis of FIERCE-22
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract