Phase 1 will evaluate the safety and tolerability at different dose levels of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by the gene ROS1 (ROS1), or neurotrophic receptor kinase genes encoding TRK kinase family (NTRK1-3) alterations to estimate the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and select the Pediatric Recommended Phase 2 Dose (RP2D).
Phase 2 will determine the anti-tumor activity of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring ROS1 or NTRK1-3 alterations.
Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
Phase 1: Age <12 years; Phase 2: Age 12- 25 years
Prior cytotoxic chemotherapy is allowed.
Prior immunotherapy is allowed.
Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
Single group
Oral repotrectinib (TPX-0005)
DrugOral repotrectinib (TPX-0005)
Dose limiting toxicities (DLTs) (Phase 1)
Define the dose limiting toxicities (DLTs) (Phase 1)
Pediatric Recommended Phase 2 Dose (RP2D) (Phase 1)
To determine the pediatric RP2D (Phase 1)
Overall Response Rate (ORR) (Phase 2)
To determine the confirmed ORR of repotrectinib (TPX-0005) as assessed by Blinded Independent Central Review (Phase 2)
Overall Response Rate (ORR) (Phase 1)
To determine the overall response rate (ORR) by Blinded Independent Central Review (BICR) (Phase 1)
Clinical Benefit Rate (CBR) (Phase 1 and Phase 2)
To determine the CBR of repotrectinib (TPX-0005) (Phase 1 and Phase 2)
Time to response (TTR) (Phase 1 and Phase 2)
To determine the TTR of reprotrectinib (TPX-005) (Phase 1 and Phase 2)
Duration of response (DOR) (Phase 1 and Phase 2)
To determine the DOR of repotrectinib (TPX-0005) (Phase 1 and Phase 2)
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