Abstract CT110: Olaparib (O) in patients (pts) with solid tumors with ATM mutation or deletion: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study
Authors: Mileham Kathryn F. , Rothe Michael , Mangat Pam K. , Garrett-Mayer Elizabeth , Yang Eddy S. , Alese Olatunji B. , Jain Angela , Duvivier Herbert L. , Palmbos Phillip , Ahn Eugene R. , Aragon-Ching Jeanny B. , Beekman Kathleen W. , Behl Deepti , Meric-Bernstam Funda , Gutierrez Rodolfo , Sanford Amy , Thota Ramya , Zakem Michael , Zhao Song , O'Lone Raegan , Grantham Gina N. , Halabi Susan , Schilsky Richard L. 
Published: June 2022

Abstract
Background: TAPUR is a phase II basket study evaluating anti-tumor 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 O are reported.
Methods: Eligible pts had solid tumors, no standard treatment (tx) options, measurable disease, ECOG Performance Status (PS) 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received O tablets (300mg) or capsules (400mg) orally twice daily until disease progression. Low accruing histology-specific cohorts with the same genomic alteration were collapsed into one histology-pooled cohort for this analysis. Primary endpoint was disease control (DC) (complete (CR) or partial (PR) response or stable disease at 16+ wks (SD16+)) (RECIST v1.1). For histology-specific cohorts a Simon 2-stage design with a null DC rate of 15% vs. 35% (power = 0.85; α = 0.10) requires 28 pts with futility stopping after 10 pts. For histology-pooled cohorts with sample size &gt; 28, if the lower limit of a one-sided 90% CI is &gt;15%, the null hypothesis of a DC rate of 15% is rejected. 2-sided 95% CIs were used for other efficacy endpoint estimates. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety.
Results: 39 pts with solid tumors (17 histologies) with ATM mut (n=36) or del (n=3) were enrolled from 6/2016 to 1/2019. 3 pts were unevaluable for efficacy. Table 1 shows demographics and outcomes. 1 CR (prostate), 2 PR (unknown primary) and 6 SD16+ were observed in pts with ATM mut for a DC rate of 25% (90% CI: 16%, 100%) and an OR rate of 8% (95% CI: 2%, 23%). The null DC rate was rejected. 9 pts had ≥1 Grade 3 tx-related adverse or serious adverse event related to O.
Conclusions: Monotherapy O showed evidence of anti-tumor activity in pts with various solid tumors with ATM mut.
Table 1. Demographics and Baseline Characteristics (N=39); Efficacy Outcomes (N=36); Toxicity Outcomes (N=39) Median (Med) age, years (range) 65 (35, 77) Female, % 46 ECOG PS, % 0 33 1 59 2 8 Prior systemic regimens, % 0 3 1 8 2 15 ≥3 74 DC rate, % (OR or SD 16+) (1-sided 90% CI) 25 (16, 100) OR rate, % (95% CI) 8 (2, 23) Med PFS, wks (95% CI) 8.4 (8.0, 15.9) Med OS, wks (95% CI) 40.4 (30.3, 50.7) Med duration OR (range), wks 18.9 (4.3, 24.4) Med duration SD16+ (range), wks 27.3 (19.4, 31.0) Number of pts1 with treatment-related adverse or serious adverse events (all Grade 3) AE2 9 SAE3 4 1Patients may have experienced one or more events2anemia, anorexia, dehydration, fatigue, hypokalemia, nausea 3colitis, dizziness, lung infection, proteinuria, urinary tract infection/obstruction
Citation Format: Kathryn F. Mileham, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Eddy S. Yang, Olatunji B. Alese, Angela Jain, Herbert L. Duvivier, Phillip Palmbos, Eugene R. Ahn, Jeanny B. Aragon-Ching, Kathleen W. Beekman, Deepti Behl, Funda Meric-Bernstam, Rodolfo Gutierrez, Amy Sanford, Ramya Thota, Michael Zakem, Song Zhao, Raegan O'Lone, Gina N. Grantham, Susan Halabi, Richard L. Schilsky. Olaparib (O) in patients (pts) with solid tumors with ATM mutation or deletion: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT110.