A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations

November 18, 2025 updated by: Turning Point Therapeutics, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Enrollment of subjects into Phase 1 will proceed concurrently by age as follows:

  • Subjects <12 years old will initially be enrolled in the Phase 1 part to determine the pediatric RP2D for this age group; once the pediatric RP2D is determined, subjects age <12 years old may be enrolled into the Phase 2 part of the study.
  • Subjects 12 to 25 years old will be directly enrolled into the Phase 2 part concurrent with Phase 1 enrollment.

Phase 1:

Approximately 12 pediatric subjects with locally advanced or metastatic solid tumors, including a primary central nervous system (CNS) tumor, or anaplastic large cell lymphoma (ALCL), with disease progression or who are non-responsive or intolerant to available therapies and for which no standard or available curative therapy exists.

Phase 2:

Subjects will be enrolled in one of 3 cohorts as follows:

Cohort 1: approximately 10-20 subjects with solid tumors characterized by NTRK fusion, TRK tyrosine kinase inhibitor (TKI)-naïve, and centrally confirmed measurable disease at baseline.

Cohort 2: approximately 23 subjects with solid tumors characterized by NTRK fusion, TRK TKI-pretreated, and centrally confirmed measurable disease at baseline.

Cohort 3: approximately 20 subjects with solid tumors or ALCL characterized by other ALK/ROS1/NTRK alterations or NTRK fusions without centrally confirmed measurable disease not otherwise eligible for Cohort 1 or 2. As of the current protocol amendment, only patients with ROS1 alterations will be enrolled to this cohort.

Study Type

Interventional

Enrollment (Estimated)

75

Phase

  • Phase 2
  • Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: BMS Study Connect Contact Center www.BMSStudyConnect.com
  • Phone Number: 855-907-3286
  • Email: Clinical.Trials@bms.com

Study Contact Backup

  • Name: First line of the email MUST contain the NCT# and Site #.

Study Locations

  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Recruiting
        • Local Institution - 6104
        • Contact:
          • Site 6104
      • Westmead, New South Wales, Australia
        • Completed
        • Local Institution - 6103
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Recruiting
        • Children's Health Queensland Hospital and Health Service
        • Contact:
          • Timothy Hassall, Site 6102
          • Phone Number: 61730681111
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Recruiting
        • Perth Childrens Hospital
        • Contact:
          • Nick Gottardo, Site 6101
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T3B 6A8
        • Recruiting
        • University of Calgary
        • Contact:
          • Victor Lewis, Site 2202
          • Phone Number: 14039557203
      • Edmonton, Alberta, Canada, T6G 2B7
        • Recruiting
        • Stollery Children's Hospital
        • Contact:
          • Sunil desai, Site 2201
          • Phone Number: 17802485415
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L1
        • Recruiting
        • Children's Hospital of Eastern Ontario
        • Contact:
          • Lesleigh Abbott, Site 2203
          • Phone Number: 61373776002370
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Recruiting
        • St Justine Hospital
        • Contact:
          • Sebastien Perreault, Site 2205
          • Phone Number: 4384958893
  • Denmark
      • Copenhagen, Denmark, 2100
        • Recruiting
        • Rigshospitalet - Glostrup
        • Contact:
          • Karsten Nysom, Site 4901
          • Phone Number: 4535450809
  • France
      • Angers, France, 49933
        • Recruiting
        • Centre Hospitalier Universitaire d'Angers
        • Contact:
          • Emilie De Carli, Site 4203
          • Phone Number: 0241353863
      • Bordeaux, France, 33076
        • Recruiting
        • Centre Hospitalier Universitaire de Bordeaux - Groupe Hospitalier Pellegrin
        • Contact:
          • Stephane Ducassou, Site 4201
          • Phone Number: 0557820438
      • Lyon, France, 69373
        • Recruiting
        • Institut d Hematologie et d Oncologie Pediatriques
        • Contact:
          • Nadege Corradini, Site 4204
          • Phone Number: 33478782642
      • Marseille, France, 13385
        • Recruiting
        • Hôpitaux Universitaires de Marseille Timone
        • Contact:
          • Nicolas Andre, Site 4205
          • Phone Number: 33491386821
      • Marseille, France, 13385
        • Not yet recruiting
        • Local Institution - 6110
        • Contact:
          • Site 6110
      • Nantes, France, 44093
        • Not yet recruiting
        • Local Institution - 6112
        • Contact:
          • Site 6112
      • Paris, France, 75005
        • Not yet recruiting
        • Local Institution - 6109
        • Contact:
          • Site 6109
      • Villejuif, France, 94805
        • Not yet recruiting
        • Local Institution - 6108
        • Contact:
          • Site 6108
      • Villejuif, France, 94805
        • Recruiting
        • Institut Gustave-Roussy
        • Contact:
          • Samuel Abbou, Site 4202
          • Phone Number: 142114211
    • Rhone
      • Lyon, Rhone, France, 69008
        • Not yet recruiting
        • Local Institution - 6111
        • Contact:
          • Site 6111
  • Italy
      • Milan, Italy, 20133
        • Recruiting
        • Fondazione IRCCS - Istituto Nazionale dei Tumori
        • Contact:
          • Michela Casanova, Site 4301
          • Phone Number: 390223902593
      • Padua, Italy, 35128
        • Withdrawn
        • Local Institution - 6113
      • Rome, Italy, 00165
        • Not yet recruiting
        • Local Institution - 4302
        • Contact:
          • Site 4302
      • Torino, Italy, 10126
        • Withdrawn
        • Local Institution - 6114
  • Singapore
      • Singapore, Singapore, 229899
        • Recruiting
        • KK Women's and Children's Hospital
        • Contact:
          • Shui Yen Soh, Site 6402
          • Phone Number: 6563941045
      • Singapore, Singapore, 119228
        • Recruiting
        • National University Hospital
        • Contact:
          • Allen Yeoh, Site 6401
          • Phone Number: 67724406
  • South Korea
      • Seoul, South Korea, 05505
        • Recruiting
        • Asan Medical Center
        • Contact:
          • Kyung Nam Koh, Site 6302
          • Phone Number: +82230105994
      • Seoul, South Korea, 03080
        • Recruiting
        • Seoul National University Hospital
        • Contact:
          • Hyoung Jin Kang, Site 6301
          • Phone Number: 82220723304
      • Seoul, South Korea, 06351
        • Completed
        • Local Institution - 6304
    • Seodaemun-gu
      • Seoul, Seodaemun-gu, South Korea, 03722
        • Completed
        • Local Institution - 6303
  • Spain
      • Barcelona, Spain, 8035
        • Recruiting
        • Hospital Universitari Vall d'Hebron
        • Contact:
          • Maria Paula Perez Albert, Site 4103
      • Barcelona, Spain, 08014
        • Not yet recruiting
        • Local Institution - 6105
        • Contact:
          • Site 6105
      • Madrid, Spain, 28009
        • Recruiting
        • Hospital Infantil Universitario Nino Jesus
        • Contact:
          • Alvaro Lassaletta, Site 4105
          • Phone Number: +34915035938
      • Madrid, Spain, 28022
        • Recruiting
        • Clinica Universidad de Navarra
        • Contact:
          • Elena Panizo Morgado, Site 4101
          • Phone Number: 34913531920
      • Madrid, Spain, 28009
        • Not yet recruiting
        • Local Institution - 6106
        • Contact:
          • Site 6106
      • Madrid, Spain, 28050
        • Recruiting
        • HM Sanchinarro University Hospital
        • Contact:
          • Marta Osuna Marco, Site 4104
          • Phone Number: 34917089935
      • Seville, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen del Rocio
        • Contact:
          • Jose Luis Moreno, Site 4108
          • Phone Number: 955012000
      • Valencia, Spain, 46026
        • Recruiting
        • Hospital Universitario y Politecnico La Fe
        • Contact:
          • Antonio Juan Ribelles, Site 4107
          • Phone Number: 961244190
      • Valencia, Spain, 46026
        • Not yet recruiting
        • Local Institution - 6107
        • Contact:
          • Site 6107
    • Barcelona
      • Esplugues de Llobregat, Barcelona, Spain, 08950
        • Recruiting
        • Hospital Sant Joan de Deu
        • Contact:
          • Alicia Castaneda Heredia, Site 4106
          • Phone Number: 34932532100
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Recruiting
        • Clinica Universidad de Navarra
        • Contact:
          • Elena Panizo Morgado, Site 4102
          • Phone Number: 34913531920
  • Taiwan
      • Taipei, Taiwan, 11031
        • Recruiting
        • Taipei Medical University Hospital
        • Contact:
          • Yen-Lin Liu, Site 6201
          • Phone Number: 886970749572
      • Taipei, Taiwan, 100225
        • Recruiting
        • National Taiwan University Hospital
        • Contact:
          • Shiann-Tarng Jou, Site 6202
          • Phone Number: 886223123456x71716
  • United Kingdom
      • Birmingham, United Kingdom, B4 6DH
        • Completed
        • Local Institution - 4403
      • Cardiff, United Kingdom, CF14 4XW
        • Recruiting
        • University Hospital of Wales
        • Contact:
          • Madeleine Adams, Site 4401
          • Phone Number: 02920742107
      • Glasgow, United Kingdom, G51 4TF
        • Recruiting
        • Royal Hosp. for Children
        • Contact:
          • Milind Ronghe, Site 4406
      • London, United Kingdom, SW3 6JJ
        • Recruiting
        • The Royal Marsden NHS Foundation Trust
        • Contact:
          • Linley Marchall, Site 4405
          • Phone Number: 209156161
      • London, United Kingdom, WC1N 3JH
        • Recruiting
        • Great Ormond Street Hospital for Children NHS Foundation Trust
        • Contact:
          • Elwira Szychot, Site 4402
          • Phone Number: 447849760509
    • England
      • Liverpool, England, United Kingdom, L12 2AP
        • Recruiting
        • Alder Hey Children's NHS Foundation Trust
        • Contact:
          • Lisa Howell, Site 4404
          • Phone Number: +441512933679
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California at Los Angeles
        • Contact:
          • Noah Federman, Site 2109
          • Phone Number: 310-206-7625
      • Los Angeles, California, United States, 90027-6062
        • Recruiting
        • Children's Hospital Los Angeles
        • Contact:
          • Leo Mascarenhas, Site 2111
          • Phone Number: 323-361-5418
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • Children's Hospital Colorado - Anschutz Medical Campus
        • Contact:
          • Margaret Macy, Site 2108
          • Phone Number: 720-777-8856
    • Florida
      • Orlando, Florida, United States, 32827
        • Completed
        • Local Institution - 2120
      • Orlando, Florida, United States, 32806
        • Completed
        • Local Institution - 2105
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Recruiting
        • Children's Healthcare of Atlanta - Egleston Hospital
        • Contact:
          • Tobey Macdonald, Site 2119
          • Phone Number: 000-000-0000
    • Maine
      • Scarborough, Maine, United States, 04074
        • Recruiting
        • Maine Medical Center
        • Contact:
          • Stanley Chaleff, Site 2115
          • Phone Number: 207-396-7565
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana Farber Cancer Institute.
        • Contact:
          • Steven Dubois, Site 2106
          • Phone Number: 415-476-3831
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine in St. Louis
        • Contact:
          • Andrew Cluster, Site 2113
          • Phone Number: 443-745-4180
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Completed
        • Local Institution - 2110
    • New York
      • New York, New York, United States, 10065
        • Completed
        • Local Institution - 2102
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Recruiting
        • Levine Children's Hospital- Pediatric Neuro-Oncology
        • Contact:
          • Chad Jacobsen, Site 2121
          • Phone Number: 000-000-0000
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Completed
        • Local Institution - 2112
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Completed
        • Local Institution - 2114
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia-Center for Childhood Cancer Research
        • Contact:
          • Theodore Laetsch, Site 2117
          • Phone Number: 267-425-5544
    • Tennessee
      • Memphis, Tennessee, United States, 38015
        • Recruiting
        • St. Jude Children's Research Hospital
        • Contact:
          • Alberto Pappo, Site 2103
          • Phone Number: 901-595-3300
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • The University of Texas Southwestern Medical Center - Harold C Simmons Comprehensive Cancer Center
        • Contact:
          • Tanya Carens Watt, Site 2101
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine
        • Contact:
          • Matthew McEvoy, Site 2118
      • Houston, Texas, United States, 77030
        • Completed
        • Local Institution - 2104
    • Virginia
      • Richmond, Virginia, United States, 23219
        • Withdrawn
        • Children's Hospital of Richmond at VCU

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Repotrectinib (TPX-0005)

Phase 1

Oral repotrectinib (TPX-0005):

Safety and tolerability at different dose levels

Phase 2

Oral repotrectinib (TPX-0005): 3 cohorts

Cohort 1: TKI-naive NTRK fusion Cohort 2: Prior TKI NTRK fusion Cohort 3: ROS1 gene fusions or other ROS1 aberrations
Drug: Oral repotrectinib (TPX-0005)
Oral repotrectinib (TPX-0005)
Other Names:
  • repotrectinib
  • Oral repotrectinib (TPX-0005) capsules
  • Oral repotrectinib (TPX-0005) oral suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose limiting toxicities (DLTs) (Phase 1)
Time Frame: Within 28 days of the first repotrectinib dose
Define the dose limiting toxicities (DLTs) (Phase 1)
Within 28 days of the first repotrectinib dose
Pediatric Recommended Phase 2 Dose (RP2D) (Phase 1)
Time Frame: Within 28 days of the last patient dosed in escalation
To determine the pediatric RP2D (Phase 1)
Within 28 days of the last patient dosed in escalation
Overall Response Rate (ORR) (Phase 2)
Time Frame: Two to three years after first dose of repotrectinib
To determine the confirmed ORR of repotrectinib (TPX-0005) as assessed by Blinded Independent Central Review (Phase 2)
Two to three years after first dose of repotrectinib

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS) (Phase 2)
Time Frame: Approximately three years
To determine the OS (Phase 2)
Approximately three years
Overall Response Rate (ORR) (Phase 1)
Time Frame: Approximately three years
To determine the overall response rate (ORR) by Blinded Independent Central Review (BICR) (Phase 1)
Approximately three years
Clinical Benefit Rate (CBR) (Phase 1 and Phase 2)
Time Frame: Approximately three years
To determine the CBR of repotrectinib (TPX-0005) (Phase 1 and Phase 2)
Approximately three years
Time to response (TTR) (Phase 1 and Phase 2)
Time Frame: Approximately three years
To determine the TTR of reprotrectinib (TPX-005) (Phase 1 and Phase 2)
Approximately three years
Duration of response (DOR) (Phase 1 and Phase 2)
Time Frame: Approximately three years
To determine the DOR of repotrectinib (TPX-0005) (Phase 1 and Phase 2)
Approximately three years
Intracranial objective response rate (IC-ORR) (Phase 1 and Phase 2)
Time Frame: Approximately three years
To determine the IC-ORR of repotrectinib (TPX-005) (Phase 1 and Phase 2)
Approximately three years
Central Nervous System Progression-Free Survival (CNS-PFS) (Phase 2)
Time Frame: Approximately three years
CNS-PFS in subjects with measurable brain metastases (Phase 2)
Approximately three years
Progression-free survival (PFS) (Phase 2)
Time Frame: Approximately three years
To determine the PFS (Phase 2)
Approximately three years
Maximum concentration of repotrectinib in plasma (Cmax)
Time Frame: Pre-dose and up to 24 hours post-dose on Day 1 and Day 15 in Cycle 1 (each cycle is 28 days)
To determine the Cmax
Pre-dose and up to 24 hours post-dose on Day 1 and Day 15 in Cycle 1 (each cycle is 28 days)
Area under the concentration versus time curve of repotrectinib in plasma (AUC)
Time Frame: Pre-dose and up to 24 hours post-dose on Day 1 and Day 15 in Cycle 1 (each cycle is 28 days)
To determine the AUC
Pre-dose and up to 24 hours post-dose on Day 1 and Day 15 in Cycle 1 (each cycle is 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Turning Point Therapeutics, Inc.

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 12, 2020

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

September 30, 2027

Study Registration Dates

First Submitted

September 12, 2019

First Submitted That Met QC Criteria

September 17, 2019

First Posted (Actual)

September 19, 2019

Study Record Updates

Last Update Posted (Estimated)

November 19, 2025

Last Update Submitted That Met QC Criteria

November 18, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA127-1029 (Other Identifier: BMS Protocol ID)
  • TPX-0005-07 (Other Identifier: Turning Point Therapeutics Protocol ID)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There are no plans to share individual participant data with other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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