A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements

Summary

Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose (RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction. Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) of repotrectinib in each subject population expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. The secondary objective will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.

Timeline

Start

2017-03-07

Primary completion

2028-02-29

Completion

2028-02-29

Publications

• Besse B, Lin JJ, Bazhenova L, Goto K, de Langen AJ, Kim DW, Wolf J, Springfeld C, Popat S, Lim DWT, Nagasaka M, Hong JY, Baik CS, Hervieu A, Moreno V, Yang N, Kollengode K, Yang H, Xu Y, Calvet CY, Yuan Y, Hammell AB, Drilon A, Solomon BJ. Repotrectinib in NTRK fusion-positive advanced solid tumors: a phase 1/2 trial. Nat Med. 2026 Feb;32(2):682-689. doi: 10.1038/s41591-025-04079-7. Epub 2026 Feb 4.
• Ajani JA, D'Amico TA, Bentrem DJ, Corvera CU, Das P, Enzinger PC, Enzler T, Gerdes H, Gibson MK, Grierson P, Gupta G, Hofstetter WL, Ilson DH, Jalal S, Kim S, Kleinberg LR, Klempner S, Lacy J, Lee B, Licciardi F, Lloyd S, Ly QP, Matsukuma K, McNamara M, Merkow RP, Miller AM, Mukherjee S, Mulcahy MF, Perry KA, Pimiento JM, Reddi DM, Reznik S, Roses RE, Strong VE, Su S, Uboha N, Wainberg ZA, Willett CG, Woo Y, Yoon HH, McMillian NR, Stein M. Gastric Cancer, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology. J Natl Compr Canc Netw. 2025 May;23(5):169-191. doi: 10.6004/jnccn.2025.0022.
• Drilon A, Camidge DR, Lin JJ, Kim SW, Solomon BJ, Dziadziuszko R, Besse B, Goto K, de Langen AJ, Wolf J, Lee KH, Popat S, Springfeld C, Nagasaka M, Felip E, Yang N, Velcheti V, Lu S, Kao S, Dooms C, Krebs MG, Yao W, Beg MS, Hu X, Moro-Sibilot D, Cheema P, Stopatschinskaja S, Mehta M, Trone D, Graber A, Sims G, Yuan Y, Cho BC; TRIDENT-1 Investigators. Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024 Jan 11;390(2):118-131. doi: 10.1056/NEJMoa2302299.
• Yun MR, Kim DH, Kim SY, Joo HS, Lee YW, Choi HM, Park CW, Heo SG, Kang HN, Lee SS, Schoenfeld AJ, Drilon A, Kang SG, Shim HS, Hong MH, Cui JJ, Kim HR, Cho BC. Repotrectinib Exhibits Potent Antitumor Activity in Treatment-Naive and Solvent-Front-Mutant ROS1-Rearranged Non-Small Cell Lung Cancer. Clin Cancer Res. 2020 Jul 1;26(13):3287-3295. doi: 10.1158/1078-0432.CCR-19-2777. Epub 2020 Apr 8.
• Drilon A, Ou SI, Cho BC, Kim DW, Lee J, Lin JJ, Zhu VW, Ahn MJ, Camidge DR, Nguyen J, Zhai D, Deng W, Huang Z, Rogers E, Liu J, Whitten J, Lim JK, Stopatschinskaja S, Hyman DM, Doebele RC, Cui JJ, Shaw AT. Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations. Cancer Discov. 2018 Oct;8(10):1227-1236. doi: 10.1158/2159-8290.CD-18-0484. Epub 2018 Aug 9.

Drugs

Indications