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Treatment with repotrectinib for young patients with specific genetic alterations in tumors

A Phase 1/2, Open-Label, Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity Study of Repotrectinib in Pediatric and Young Adult Subjects With Advanced or Metastatic Malignancies Harboring ALK, ROS1, NTRK1-3 Alterations

Phase1; Phase2 Interventional Turning Point Therapeutics, Inc. · NCT04094610

This study is testing a new oral medication called repotrectinib to see if it can help young patients with advanced tumors that have certain genetic changes when other treatments haven't worked.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment75 (estimated)
AgesN/A to 25 Years
SexAll
SponsorTurning Point Therapeutics, Inc. Industry-sponsored
Drugs / interventionsrepotrectinib, chemotherapy, immunotherapy
Locations68 sites (Los Angeles, California and 67 other locations)
Trial IDNCT04094610 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of repotrectinib, an oral medication, in pediatric and young adult patients with advanced or metastatic solid tumors that have specific genetic alterations involving ALK, ROS1, or NTRK1-3. The study is divided into two phases: Phase 1 focuses on determining the maximum tolerated dose in younger patients, while Phase 2 assesses the anti-tumor activity of the drug in a broader age group. Participants will be enrolled based on their age and specific tumor characteristics, with a focus on those who have not responded to existing therapies.

Who should consider this trial

Good fit: Ideal candidates are pediatric and young adult patients aged 12 to 25 with advanced or metastatic tumors that have documented genetic alterations in ALK, ROS1, or NTRK1-3.

Not a fit: Patients without the specified genetic alterations or those who are older than 25 years may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for young patients with difficult-to-treat tumors harboring specific genetic alterations.

How similar studies have performed: Other studies have shown promise with targeted therapies for similar genetic alterations, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

1. 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.
2. Phase 1: Age \<12 years; Phase 2: Age 12- 25 years
3. Prior cytotoxic chemotherapy is allowed.
4. Prior immunotherapy is allowed.
5. Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
6. All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
7. Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
8. Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
9. Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
10. Adequate hematologic, renal and hepatic function.

Phase 2 Inclusion Criteria:

1. Cohort Specific Inclusion Criteria:

   * Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
   * Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
   * Cohort 3: subjects with advanced solid tumors with ROS1 gene fusions or other ROS1 aberrations (including amplifications and point mutations) with measurable disease.
2. Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment.

Key Exclusion Criteria (Phase 1 and Phase 2):

1. Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
2. 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.
3. Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
4. Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
5. Any of the following cardiac criteria:

   * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value
   * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec)
   * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
6. Peripheral neuropathy of CTCAE ≥grade 2.
7. Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
8. Any potential allergies to repotrectinib and/or its excipients.

Where this trial is running

Los Angeles, California and 67 other locations

+18 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Locally Advanced Solid TumorsMetastatic Solid TumorsLymphomaPrimary CNS TumorsALKROS1NTRK1-3Primary CNS tumor
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.