A phase I study of the type II ROS1 TRK inhibitor ANS03 in ROS1 fusion-positive lung cancers
Presenter: Shengxiang Ren Session: First-in-Human Phase I Clinical Trials Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
Alexander Drilon 1 , Jia Yu 2 , Zhiyong He 3 , Yongsheng Wang 4 , Kejing Tang 5 , Tianqing Chu 2 , Shutan Liao 6 , Junjun Zhang 7 , Xinlong Zheng 8 , Jaime Rubio-Perez 9 , Matteo Repetto 9 , Brendan Putz 10 , Shengxiang Ren 8 1 Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, 2 Shanghai Chest Hospital, Shanghai, China, 3 Fujian Cancer Hospital, Fuzhou, China, 4 West China Hospital of Sichuan University, Chengdu, China, 5 The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, 6 Avistone Biotechnology Ltd.,, Beijing, China, 7 Avistone Biotechnology Ltd, Beijing, China, 8 Shanghai Pulmonary Hospital, Shanghai, China, 9 Memorial Sloan Kettering Cancer Center, New York, NY, 10 Avistone Biotechnology, Inc., USA, Dover, DE
Abstract
Background: ROS1 tyrosine kinase inhibitors (TKIs) are highly effective in ROS1 -positive non-small cell lung cancer (NSCLC), but acquired resistance remains a challenge, particularly solvent front (SF) mutations like G2032R and D2033N, and the central beta sheet (Cβ6) mutation L2086F. ANS03 is a next generation type II TKI targeting both ROS1 and TRK, possessing a broad spectrum of acquired drug-resistant mutation coverage. In preclinical studies, ANS03 was more potent than repotrectinib against SF mutations and more potent than repotrectinib or zidesamtinib against L2086F. Method: A phase 1 study (NCT06716138) was designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ANS03 in participants with locally advanced or metastatic solid tumors harboring a ROS1 or NTRK alteration. Dose escalation was determined by Bayesian optimal interval design. Response was assessed by investigators using RECIST V1.1. Results: As of January 6, 2026, the dose escalation study is ongoing. Five dose levels (15mg qd, 30mg qd, 45mg qd, 67.5mg qd and 90mg qd) have been completed. A total of 20 NSCLC patients harboring ROS1/NTRK fusions were enrolled. No dose-limiting toxicities were observed. The most frequently reported treatment related adverse events (TRAE) were low grade, including the elevation of AST/ALT (80%), bilirubin (35%) and LDH (35%). Grade ≥3 TRAE occurred in 25% of patients. Only low grade neurotoxicities (15%) including dizziness, dysgeusia and pain in the limbs occurred. Among 18 efficacy evaluable ROS1 fusion-positive cancers, objective response rates (ORRs) were 38.8% (7/18) for all enrolled patients and 54.5% (6/11) for patients previously received ≥2L systemic therapy and at least 1 prior ROS1 TKI. Of the latter, six patients were pre-treated with 2-4 ROS1 TKIs including lorlatinib, repotrectinib, taletrectinib, and zidesamtinib. Among heavily pretreated patients, one patient posted 5 prior lines of systemic therapy (3 prior TKIs) with an L2086F mutant cancer had a confirmed partial response (PR) with ANS03 at 12 weeks. Two additional patients who received ≥6 prior lines of systemic therapy and ≥4 prior TKIs had a PR at the first tumor assessment and remain on ANS03 therapy. Conclusions: ANS03 had a manageable safety profile with a low incidence of neurotoxicity. In ROS1 fusion-positive NSCLCs, promising preliminary anti-tumor activity was achieved, including against ROS1 L2086F.
Disclosure
A. Drilon, None.. J. Yu, None.. Z. He, None.. Y. Wang, None.. K. Tang, None.. T. Chu, None.. S. Liao, None.. J. Zhang, None.. X. Zheng, None. J. Rubio-Perez, Alfonso Mart?n Escudero Foundation ). Takeda Other, Advisory. MSD, Pfizer, Roche, Lilly, Eisai, Persan and Astra Zeneca Other, Speaker fees. M. Repetto, OncLive Other, Advisory board. B. Putz, None.. S. Ren, None.
Cited in
Control: 11212 · Presentation Id: 12079 · Meeting 21436