MyTACTIC: Activity of Targeted Therapy in Patients (pts) with Advanced Solid Tumors Harboring Specific Biomarkers.

3100 Background: MyTACTIC (NCT04632992) is a tumor-agnostic, non-randomized, open-label phase II basket trial evaluating the activity of targeted therapies, alone or in combination, in pts with advanced solid tumors carrying potentially actionable molecular alterations. We report pt outcomes across all arms of the MyTACTIC trial. Methods: Eligible pts were ≥18 years old, had an ECOG PS ≤2, and measurable or evaluable lesions per RECIST v1.1 with one or more of these actionable oncogenic biomarkers: ROS1, PIK3CA, ALK, AKT, PTEN, TMB, MSI/dMMR, ERBB2,and RET. Alterations were identified prior to enrolment using local testing, typically by next-generation sequencing. Pts who had previously received the study drug or had symptomatic or active CNS metastases were excluded. Prior targeted therapy other than trial agents was allowed. Pts were assigned to 1 of 15 treatment arms to receive single-agent or combined targeted therapy according to positive biomarker results. The primary outcome was investigator-assessed confirmed objective response rate (cORR). Safety was assessed in all treated pts. Results: At data cut-off (Jan 12, 2024), 252 pts were enrolled into one of 14 arms; no pts were enrolled into arm A (entrectinib in ROS1fusion-positive tumors). Overall, pts had a median age of 65 years (range 34–90) and 93% of them had an ECOG PS ≤1. Median follow-up was 8.3 months (range 0.7–32.0). Responses were observed across 7 arms, with a cORR ranging from 11.5% to 66.7% (Table); no responses were seen in arms G, H, J, K, and L. Further efficacy outcomes including progression-free survival, duration of response, and disease control rate will be reported for each arm. The safety profile of each drug or drug combination was as expected based on prior reports. Conclusions: Targeted therapies yielded responses across tumor types in most treatment arms; testing for actionable molecular alterations is warranted for pts with limited treatment options. Clinical trial information: NCT04632992 . [Table: see text]