1807P - Talazoparib (TALA) plus enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC): Subgroup analyses of the all-comers cohort from TALAPRO-2 by homologous recombination repair (HRR) status

Background

The randomized, Phase 3, placebo (PBO)-controlled TALAPRO-2 study demonstrated statistically significant improvements in radiographic progression-free survival (rPFS) for 1st-line TALA + ENZA vs PBO + ENZA in patients (pts) with mCRPC in all-comers and in HRR subgroups (HRR-deficient [HRR+] and HRR-non-deficient [HRR-] or unknown). Here, we report baseline characteristics and secondary efficacy and safety endpoints for all-comers by HRR status.

Methods

Pts randomized 1:1 to TALA 0.5 mg or PBO, + ENZA 160 mg/day, were stratified by prior abiraterone or docetaxel for castration-sensitive PC (yes vs no) and by HRR status (HRR+ vs HRR-/unknown). The primary endpoint was rPFS by BICR per RECIST 1.1/PCWG3. Secondary endpoints included overall survival (OS), objective response rate (ORR), time to PSA progression, time to initiation of cytotoxic chemotherapy, time to progression on first subsequent antineoplastic therapy or death (PFS2), and safety.

Results

Of 805 enrolled pts, all had prospective tumor tissue HRR test results. Overall, baseline characteristics were relatively well-balanced between treatment groups and by HRR status; however, in the younger group (age <65 y), there were more HRR+ (29.6%) than HRR-/unknown (19.3%) pts, and HRR+ pts had evidence of more aggressive disease (Table). Treatment with TALA + ENZA improved ORR, and prolonged time to PSA progression; time to initiation of cytotoxic chemotherapy; and PFS2 vs PBO + ENZA, with benefit seen in both HRR+ and HRR-/unknown subgroups (Table). OS remains immature. Further data will be presented on baseline characteristics, efficacy, and TEAEs by treatment group for HRR+ and HRR-/unknown subgroups.

Table: 1807P

P values 2-sided

Conclusions

TALA + ENZA demonstrated improvements in secondary efficacy endpoints over PBO + ENZA as 1st-line treatment in pts with mCRPC in both HRR+ and HRR-/unknown subgroups.

Clinical trial identification

NCT03395197.

Editorial acknowledgement

Medical writing support was provided by Annette Smith, PhD, of CMC Affinity, a division of IPG Health Medical Communications.

Legal entity responsible for the study

Pfizer is responsible for the governance, coordination and running of the study.

Funding

This study was funded by Pfizer Inc. Astellas Pharma Inc. provided enzalutamide.

Disclosure

N. Matsubara: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Coordinating PI: Janssen, Roche, MSD, Taiho, Pfizer, Chugai; Financial Interests, Institutional, Local PI: AstraZeneca, Bayer, Astellas, Amgen, Eisai, Eli Lilly, AbbVie. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Personal, Advisory Board, February 2022: Arvinas; Financial Interests, Personal, Advisory Board, April 2022: Macrogenics; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the CAPITELLO 281 phase 3 trial: AstraZeneca; Non-Financial Interests, Principal Investigator, Chair of the TALAPRO-2 and TALAPRO-3 phase 3 trials: Pfizer; Non-Financial Interests, Principal Investigator, Chair of the RADIANT phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the TRITON-3 phase 3 trial: Clovis. A.A. Azad: Financial Interests, Personal, Advisory Board: Astellas, Novartis, Sanofi, AstraZeneca, Tolmar, Telix, Merck Serono, Janssen, BMS, Ipsen, Bayer, Pfizer, Amgen, Noxopharm, Merck Sharpe Dohme; Financial Interests, Personal, Other, Consultant: Aculeus Therapeutics; Financial Interests, Personal, Invited Speaker: Astellas, Janssen, Novartis, Amgen, Ipsen, BMS, Merck Serono, Bayer; Financial Interests, Personal, Other, Travel + Accommodation: Astellas, Merck Serono, Amgen, Novartis, Janssen, Tolmar, Pfizer, Bayer; Financial Interests, Personal, Research Grant: Astellas, Merck Serono, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Astellas, Pfizer, Exelixis; Financial Interests, Institutional, Local PI: BMS, Aptevo Therapeutics, AstraZeneca, GSK, Pfizer, Astellas, SYNthorx, Bionomics, Sanofi, Ipsen, Exelixis, Merck Sharpe Dohme, Janssen, Eli Lilly, Gilead Sciences, Merck Serono, Hinova; Financial Interests, Institutional, Trial Chair: Bayer; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Hinova; Non-Financial Interests, Leadership Role, Chair, Translational Research Committee: ANZUP Cancer Trials Group; Non-Financial Interests, Leadership Role, Member, Scientific Advisory Committee: ANZUP Cancer Trials Group; Non-Financial Interests, Leadership Role, Chair, Urologic Oncology Committee: Clinical Oncology Society of Australia; Non-Financial Interests, Other, Editorial Board Member: BMC Urology; Non-Financial Interests, Other, Associate Editor: Cancer Research Communications, Frontiers in Oncology. J. Carles Galceran: Financial Interests, Personal, Advisory Board: Astellas Pharma, AstraZeneca, Bayer, Johnson & Johnson, MSD Oncology, Novartis (AAA), Roche, Sanofi; Financial Interests, Institutional, Local PI: Janssen Cilag International NV, Lilly, S.A, Medimmune, Novartis Farmacéutica, S.A, Sanofi-Aventis, S.A; Other, Other, Member of the Comission: Catalan Program of Ambulatory Medication Comission (CAHMDA). A.P. Fay: Financial Interests, Personal, Royalties: Astellas Pharma, AstraZeneca, BMS, Ipsen, Janssen, MSD, Novartis, Pfizer, and Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Bayer, Ipsen, Janssen, MSD, Novartis, Pfizer, and Roche; Financial Interests, Personal, Stocks or ownership: Brazilian Information Oncology; Financial Interests, Personal, Research Funding: AstraZeneca, BMS, CAPES – CNPq, Foundation Medicine, Ipsen, MSD, and Roche; Financial Interests, Personal, Other, Travel & Accommodations: Astellas Pharma, AstraZeneca, BMS, Ipsen, Janssen, MSD, Novartis, Pfizer, and Roche. U.F.F. De Giorgi: Financial Interests, Personal, Advisory Board: Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, Eisai, Janssen; Financial Interests, Personal, Invited Speaker: Roche, BMS, Clovis Oncology, AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca, Sanofi, Roche. P.C. Fong: Financial Interests, Personal, Speaker, Consultant, Advisor: MSD; Financial Interests, Personal, Other, Travel: Pfizer. R.J. Jones: Financial Interests, Personal, Royalties, Honoraria: Astellas Pharma, Bayer, BMS, Ipsen, Janssen, Merck Serono, MSD, Pfizer, and Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas Pharma, Bayer, BMS, Ipsen, Janssen, Merck Serono, MSD, Novartis, Pfizer, and Roche; Financial Interests, Personal, Research Funding: Astellas Pharma, Bayer, Clovis Oncology, Exelixis, and Roche; Financial Interests, Personal, Other, Travel & Accommodation: Bayer and Janssen. N.D. Shore: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boston Scientific, Clovis Oncology, Cold Genesys, Dendreon, Exact Imaging, Exact Sciences, FerGene, Genesis Care Us, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad, Nymox, Pacific Edge, Pfizer, Propella, PreView, Sanofi Genzyme, Speciality Networks, Sesen Bio, Tolmar, Urogen, Clarity, Lantheus, Lilly, Photocure, Telix, Photocure, Vaxiion, Asieris, Alessa Therapeutics, Akido, Arquer, Fize medical, GConcology, Genentech, Guardant, Ferring, Foundation Medicine, Immunitybio, Incyte, Minomic, NGM, Nonagen, Novartis, PlatformQ, Profound, Promaxo, Protara, Vessi; Financial Interests, Personal, Member of Board of Directors: Photocure. C. Dunshee: Financial Interests, Personal, Advisory Board: Astellas Pharma, Bayer, Janssen, and Pfizer; Financial Interests, Personal, Research Funding: AstraZeneca, Bayer, Dendreon, Hengrui Pharmaceutical, Janssen, Laekna Therapeutics, Myovant Sciences, and Pfizer. S. Zschäbitz: Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Amgen, Bayer; Financial Interests, Institutional, Speaker, Consultant, Advisor: BMS, MSD, Pfizer; Financial Interests, Personal, Speaker, Consultant, Advisor: Eisai, Janssen, Novartis; Financial Interests, Personal and Institutional, Advisory Board: Amgen, Bayer; Financial Interests, Institutional, Advisory Board: BMS, MSD, Pfizer; Financial Interests, Personal, Advisory Board: Eisai, Janssen, Novartis; Financial Interests, Institutional, Research Funding: Eisai; Financial Interests, Personal, Other, travel, accommodations, and/or expenses: Amgen, Astellas Pharma, AstraZeneca, Ipsen, Janssen, Merck, MSD, and Pfizer. L.I. Karsh: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting: Astellas Pharma, AstraZeneca, Aurora Oncology, Dendreon, Ferring, Janssen, Merck, Pfizer, Sanofi, Specialty Networks/UroGPO, Vaxiion, and Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Astellas Pharma, AstraZeneca, Bayer, Janssen, Merck, Myovant, and Pfizer; Financial Interests, Personal, Principal Investigator: Astellas Pharma, AstraZeneca, Bayer, BioExcel, BMS, Dendreon, Exact Sciences, Epizyme, FKD Therapies, KDx, OncoCell, Janssen, Merck, Myovant, Pfizer, and Tavanta. P. Barthelemy: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck, Pfizer, Ipsen, Bayer, Janssen Cilag, Astellas, Novartis, Amgen, GILEAD; Financial Interests, Personal, Invited Speaker: AstraZeneca, Seagen. X. Lin, N. Di Santo: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks or ownership: Pfizer. C.G. Healy, F. Zohren: Financial Interests, Personal, Stocks or ownership: Pfizer; Financial Interests, Personal, Full or part-time Employment: Pfizer. N. Agarwal: Financial Interests, Personal, Advisory Board, In the last two calendar years, I participated in the scientific advisory board of these pharma companies between February 2021 to April 2021. None after that: Merck, Aveo, Gilead, Lilly, Exelixis, Foundation Medicine; Financial Interests, Trial Chair, I am involved in the following phase 3 trials as the trial co-chair: TALAPRO-2, TALAPRO-3 (both Pfizer), and CONTACT-2 (Exelxis): Pfizer, Exelixis; Financial Interests, Institutional, Other, I serve in the leadership of my cancer center (Huntsman Cancer Institute, University of Utah. Salt Lake City, UT, USA). There are multiple research projects sponsored by these companies which pay money to my institution: Arnivas, Astellas, AstraZeneca, Bavarian Nordic, Bayer, BMS, Calithera, Celldex, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, GSK, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon.; Financial Interests, Steering Committee Member, I am involved in the steering committee of the trials sponsored by these pharmas with no personal honorarium: AstraZeneca, Calithera, Clovis, Crispr, Eisai, Eli Lilly, Exelixis, Immunomedics, Janssen; Financial Interests, Steering Committee Member, I am involved in the steering committee of the trials sponsored by these pharma companies with no personal honorarium: Merck, Nektar, New Link Genetics, Oric, Pfizer, Prometheus, Rexahn, Takeda, and Tracon. All other authors have declared no conflicts of interest.