Abstract C149: Efficacy and safety of entrectinib in patients (pts) with locally advanced/metastatic NTRK or ROS1 fusion-positive (fp) solid tumors, not evaluable for the primary endpoint of STARTRK-2
Authors: Liu Stephen V , Peeters Marc , Ahn Myung-Ju , Lin Jessica J , Ohe Yuichiro , Yau Chung Cheung Thomas , Bordogna Walter , Osborne Stuart , Schwemmers Sven , Zeuner Harald , Goto Koichi 
Published: December 2023

Abstract
Background: Oncogenic alterations can drive the formation and progression of various solid tumor types. Entrectinib is a potent, CNS-active tyrosine kinase inhibitor that has previously demonstrated clinical activity in pts with NTRK- or ROS1-fp solid tumors in an integrated analysis of three phase I/II trials (ALKA-372-001 [EudraCT 2012-000148-88]; STARTRK-1 [NCT02097810]; STARTRK-2 [NCT02568267]). We present data from a previously unpublished cohort of pts from STARTRK-2, who were deemed non-evaluable for the primary endpoint, including a subset of pts who had non-measurable disease at baseline.
Methods: Adult pts with locally advanced/metastatic NTRK- or ROS1-fp solid tumors who received ≥1 dose of entrectinib but were considered non-evaluable for the primary endpoint of the STARTRK-2 study were included in our analyses. Pts were considered non-evaluable due to having: non-measurable disease by RECIST v1.1 at baseline per the investigator’s assessment, an Eastern Cooperative Oncology Group performance status ≥3, a history/concomitant presence of another malignancy, or dual oncogenic alterations. Tumor responses were assessed by blinded independent central review (BICR) by RECIST v1.1, at Week 4 and every 8 weeks thereafter for ≥12 months from initial on-study scan. Endpoints assessed include: objective response rate (ORR) and duration of response (DoR) by BICR, treatment duration and safety.
Results: The analysis population comprised 37 pts with solid tumors, including 19 (51.4%) with non-small cell lung cancer; 16 pts had NTRK-fp and 21 had ROS1-fp tumors. The median duration of follow-up was 52.3 months. The median age was 57 years (range 15–81) and 54% (n=20) of pts were female. The ORR by BICR was 37.8% (n/N=14/37; 95% confidence interval [CI] 22.5–55.2), including three pts with a complete response and 11 pts with a partial response. The median DoR was 35.3 months (95% CI 14.5–45.7). In the subset of pts with non-measurable disease at baseline per investigator (n=15; 41%), the median duration of follow-up was 54.3 months; the ORR by BICR was 46.7% (n/N=7/15; 95% CI 21.3–73.4) and the median DoR was 45.7 months (95% CI 45.7–not reached). The median treatment duration was 12.8 months (range 0.1–56.1) for the main analysis population (N=37) and 46.5 months (range 0.4–56.1) for the subset of pts with non-measurable disease at baseline (n=15). The safety profile (N=37) was consistent with previous reports from the integrated analysis; 32 pts (86.5%) had a treatment-related adverse event (most were Grade 1–2), without an unanticipated toxicity, and there were no treatment-related deaths.
Conclusions: Entrectinib has demonstrated clinically meaningful activity and a manageable safety profile in pts with NTRK- or ROS1-fp solid tumors who were deemed non-eligible for the primary endpoint in the STARTRK-2 study. These data suggest a potential clinical benefit with entrectinib in a group of pts who are usually excluded from clinical trials, reinforcing the need for molecular testing for all pts to optimize treatment decisions.
Citation Format: Stephen V Liu, Marc Peeters, Myung-Ju Ahn, Jessica J Lin, Yuichiro Ohe, Chung Cheung Thomas Yau, Walter Bordogna, Stuart Osborne, Sven Schwemmers, Harald Zeuner, Koichi Goto. Efficacy and safety of entrectinib in patients (pts) with locally advanced/metastatic NTRK or ROS1 fusion-positive (fp) solid tumors, not evaluable for the primary endpoint of STARTRK-2 [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C149.