Last updated on April 2020

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


Brief description of study

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 an ALK, 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 an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.

Detailed Study Description

In Phase 2, study subjects will be enrolled into 6 distinct expansion (EXP) cohorts:

  • EXP-1: ROS1 TKI-nave ROS1+ NSCLC. Up to one prior line of chemotherapy OR immunotherapy is allowed
  • EXP-2: 1 Prior ROS1 TKI ROS1+ NSCLC. Disease progression, unresponsive, or intolerant to one prior line of a ROS1 TKI. Up to one prior line of chemotherapy OR immunotherapy before or after a ROS1 TKI is allowed
  • EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC. Disease progression, unresponsive, or intolerant to 2 prior lines of a ROS1 TKI treatment. Up to one prior line of chemotherapy OR immunotherapy pre-TKI or post-TKI is allowed
  • EXP-4: ROS1 or ALK TKI-nave ROS1+ or ALK+ solid tumors (non-NSCLC). No prior ROS1 or ALK TKIs allowed. Up to 2 prior lines of chemo or immunotherapy are allowed
  • EXP-5: TRK TKI-nave NTRK+ solid tumors. Any number of prior lines of chemo or immunotherapy is allowed.
  • EXP-6: TRK TKI-pretreated NTRK+ solid tumors. Disease progression, unresponsive, or intolerant to 1 or 2 prior TRK TKIs. Any number of prior lines of chemo- or immunotherapy are allowed.

Clinical Study Identifier: NCT03093116

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