Reference Detail

Ref Type

PMID

Authors

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

Title

Olaparib (O) in patients (pts) with solid tumors with ATM mutation or deletion: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer Res	82	12_Suppl

URL

https://aacrjournals.org/cancerres/article/82/12_Supplement/CT110/701919/Abstract-CT110-Olaparib-O-in-patients-pts-with

Abstract Text

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 > 28, if the lower limit of a one-sided 90% CI is >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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
ATM mutant	Advanced Solid Tumor	conflicting	Olaparib	Phase II	Actionable	In a Phase II trial (TAPUR), Lynparza (olaparib) treatment resulted in an objective response rate of 8% and a disease control rate of 25% (9/36, 1 complete response, 2 partial responses, 6 stable disease at 16+ weeks) in patients with advanced solid tumors harboring ATM mutations (Cancer Res 2022;82(12_Suppl):Abstract nr CT110; NCT02693535).	detail...