The Royal Marsden NHS Foundation Trust, London, United Kingdom
Johann S. De Bono , Niven Mehra , Celestia S. Higano , Fred Saad , Consuelo Buttigliero , Marielena Mata , Hsiang-Chun Chen , Cynthia G. Healy , M. Luisa Paccagnella , Akos Czibere , Karim Fizazi
Background: Phase 2 and 3 studies with poly(ADP-ribose) polymerase inhibitors (PARPi) have demonstrated antitumor activity in patients (pts) with mCRPC with DDRmut who were previously treated with novel hormonal therapy (NHT). We report the first IA of a Phase 2 study of TALA, a potent inhibitor and trapper of PARP. Methods: TALAPRO-1 (NCT03148795) is enrolling pts (N ≈ 100) with measurable soft tissue disease, progressive mCRPC, and DDRmut likely to sensitize to PARPi (including ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C), who received 1–2 chemotherapy regimens (≥1 taxane-based) and progressed on ≥1 NHT (enzalutamide/abiraterone acetate). Pts receive oral TALA 1 mg/d (moderate renal impairment, 0.75 mg/d) until radiographic progression, unacceptable toxicity, or consent withdrawal. Primary endpoint is objective response rate (ORR; blinded independent review). Secondary endpoints are time to OR, duration of response, prostate-specific antigen (PSA) decrease ≥50%, circulating tumor cell (CTC) count conversion (to CTC = 0 and <5 per 7.5 mL of blood), time to PSA progression, radiographic progression-free survival (rPFS), overall survival, safety, pt-reported outcomes, and pharmacokinetics. A planned IA of safety and efficacy was performed after 20 pts with BRCA1/2 mutations were on treatment for ≥8 wks. Results: 81 pts received TALA as of June 5, 2019; 43 pts enrolled by Feb 12, 2019 were evaluable for the primary endpoint (20 BRCA1/2, 2 PALB2, 14 ATM, 7 other). All had received docetaxel and 49% prior cabazitaxel. Overall ORR (95% CI) was 25.6% (13.5–41.2), ORRBRCA1/2 50.0% (27.2–72.8), ORRATM 7.1% (0.2–33.9). Overall median (95% CI) rPFS was 5.6 months (mo) (3.5–8.2), rPFSBRCA1/2 8.2 mo (5.6–NE), rPFSATM 3.5 mo (1.7–8.1). Most common treatment-emergent adverse events (≥20%) were anemia, nausea, asthenia, decreased appetite, constipation, and platelet count decreased. Conclusions: TALA monotherapy demonstrates encouraging antitumor activity in docetaxel-pretreated mCRPC pts, especially those with BRCA1/2mut, and was generally well tolerated. This study was sponsored by Pfizer Inc. Clinical trial information: NCT03148795
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
2023 ASCO Annual Meeting
First Author: Karim Fizazi
2020 ASCO Virtual Scientific Program
First Author: Johann S. De Bono
2021 Genitourinary Cancers Symposium
First Author: Johann S. De Bono
2024 ASCO Genitourinary Cancers Symposium
First Author: Daniel Triner