Abstract CT228: Talazoparib (Tala) in patients (pts) with solid tumors with <i>ATM</i> alterations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Abstract Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with solid tumors with ATM mutation (mut) or deletion (del) treated with Tala are reported. Methods: Eligible pts had metastatic solid tumors, measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received 1 mg of Tala orally daily until disease progression. Low accruing histology-specific cohorts with ATM alterations were collapsed into 1 histology-pooled cohort for analysis. Primary endpoint was disease control (DC) per investigator defined as complete or partial response (PR) or stable disease (SD) of at least 16+ weeks (wks) duration (SD16+) per RECIST v1.1. The hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test (alpha 0.10; 82% power). Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response (OR), duration of response (DOR) and SD, and safety. Results: 29 pts with nine different solid tumors with ATM mut (n=28) or del (n=1) were enrolled. 1 pt was not evaluable for efficacy. Table shows demographics, outcomes, and toxicity. 2 PR (lung and thyroid) and 10 SD16+ (pancreas [3], prostate [2], colon, breast, kidney, rectum, stomach, thyroid) were observed in pts with ATM mut for a DC rate of 41% (1-sided 90% CI, 29 to 100) and an OR rate of 7% (95% CI, 1 to 23). The null DC rate was rejected (p=0.0005). The pt with PR and lung cancer is still on tx and has exceeded 73 wks on study as of October 2024. 8 pts had ≥1 grade 3-4 tx-related adverse event (AE). No tx-related serious AE were reported. Conclusions: Tala met prespecified criteria to declare a signal of activity in pts with solid tumors with ATM mut. Citation Format: Elie G. Dib, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Dustin Bivins, Mark Gitau, Apar K. Ganti, Arthur Winer, Vijay Suhag, Darryl Outlaw, Michael J. Hall, Olatunji B. Alese, Reza Nazemzadeh, Evan Pisick, Fengting Yan, Navid Hafez, Carmen J. Calfa, Lex Leonhardt, David DeRemer, Abigail Gregory, Dominique C. Hinshaw, Gina N. Grantham, Susan Halabi, Richard L. Schilsky. Talazoparib (Tala) in patients (pts) with solid tumors with ATM alterations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT228.