NCT05004116

A Study of Repotrectinib in Combination With Chemotherapy in Children and Young Adults With Solid Tumor Cancer

Phase 1/2 Study of TPX-0005 (Repotrectinib) in Combination With Chemotherapy in Pediatric and Young Adult Subjects With Advanced or Metastatic Solid Tumors and Primary Central Nervous System Tumors

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 77 (estimated)
• Sponsor: Memorial Sloan Kettering Cancer Center · Academic / Other
• Sex: All
• Age: 1 Year – 25 Years
• Healthy volunteers: Not accepted

Summary

This study will test the safety of the study drug, repotrectinib, in combination with chemotherapy (irinotecan and temozolomide) in children and young adults who have advanced or metastatic solid tumors. We researchers will try to find the highest dose of the study drug that causes few or mild side effects in study participants. When the researchers find this dose, we will evaluate it in a different group of participants to find out whether repotrectinib in combination with chemotherapy is an effective treatment for children and young adults who have advanced/metastatic solid tumors. Another purpose of the study is to look at the way the body absorbs, distributes, and gets rid of repotrectinib.

Detailed description

Part A : TPX-0005 (Repotrectinib) will be given orally (without regard to food) once daily for 14 days, then increased to twice daily for remainder of cycles and concurrently administered with chemotherapy backbone described below. If a patient is enrolled on DL3, cycle length will be 21 days, repotrectinib will be administered once daily x 14 days followed by twice daily if tolerated for remainder of therapy. For patients less than 12 years old or less than 50kg, adult equivalent dosing (AED) will be used Approximately 4-24 pediatric subjects will be enrolled into 2-4 dose levels (pending if DL-1 or DL-1b are utilized), with maximum of 6 subjects per dose level according to the 'rolling 6' design. Starting dose of TPX-0005 (Repotrectinib) will begin at dose level (DL) 1. Part B (PK expansion cohort for patients \<12 years old): Up to six patients \<12 years old will be included in a PK expansion cohort after the maximum tolerated dose in Part A has been determined. The number of patients included in part B will be based on the the number of patients \<12 years old enrolled on part A. A minimum of 6 patients \<12 will be included in parts A and B combined. Phase 2: Patients will be enrolled into one of the following 3 cohorts and will be treated at the RP2D of TPX-0005 (Repotrectinib) plus chemotherapy as determined in Phase 1. Cohort 1 (Neuroblastoma ALK point mutation) THIS COHORT IS CLOSED Cohort 2 (Desmoplastic Small Round Cell Tumor) Cohort 3 (Exploratory) Of note for patients enrolled to Dose Level 3 (21 day cycles), there will be no D22 assessements performed. Enrollment to Phase 2 cohort 3 will occur concurrently with Phase 1 since cohort 3 patients are being treated at the RP2D of TPX-0005 (Repotrectinib) monotherapy.

Conditions

• Advanced Cancer
• Metastatic Solid Tumor

Interventions

Type	Name	Description
DRUG	Repotrectinib	TPX-0005 (Repotrectinib) will be taken orally twice daily in 28-day cycles without regard to food and will be administered orally before administration of irinotecan and temozolomide (exception: C1, TPX-0005 (Repotrectinib) will be administered once daily x 14 days, then twice daily D15-D28).
DRUG	Irinotecan and temozolomide	Irinotecan and temozolomide will be given as per institutional standard.

Timeline

• Start date: 2021-08-09
• Primary completion: 2028-08-01
• Completion: 2028-08-01
• First posted: 2021-08-13
• Last updated: 2026-03-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study