Locally Advanced Solid TumorsPhase 1/2NCT04094610
A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
A Phase 1/2 study testing Oral repotrectinib (TPX-0005) in people with Locally Advanced Solid Tumors and Metastatic Solid Tumors, run by Turning Point Therapeutics, Inc. at 68 sites in 11 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages Up to 25 years
- Conditions the study is for
- Locally Advanced Solid Tumors, Metastatic Solid Tumors, Lymphoma
- What is being tested?
- Oral repotrectinib (TPX-0005)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 68 sitesin 11 countries
- Study dates
- 12 Mar 2020to 30 Sep 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
- 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.
- All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
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- 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.
- Subjects must have a Lansky (< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
- Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
- Adequate hematologic, renal and hepatic function.
- Phase 2 Inclusion Criteria:
- 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.
- Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment.
Who cannot join
- 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.
- 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
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- 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
- Peripheral neuropathy of CTCAE ≥grade 2.
- Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
- Any potential allergies to repotrectinib and/or its excipients.
Trial locations and contacts
68 sites in 11 countries. Contact the study team or a site near you to ask about taking part.
BMS Clinical Trials Contact Center www.BMSClinicalTrials.com contact
First line of the email MUST contain NCT # and Site #. contact
68 sites in 11 countries
United States20 sites, 12 recruiting
- Recruiting
Children's Healthcare of Atlanta - Egleston Hospital
Atlanta, Georgia, 30329
Tobey Macdonald, Site 2119, 000-000-0000
- Recruiting
Children's Hospital Colorado - Anschutz Medical Campus
Aurora, Colorado, 80045
Margaret Macy, Site 2108, 720-777-8856
- Recruiting
Dana Farber Cancer Institute.
Boston, Massachusetts, 02215
Steven Dubois, Site 2106, 415-476-3831
- Recruiting
Levine Children's Hospital- Pediatric Neuro-Oncology
Charlotte, North Carolina, 28203
Chad Jacobsen, Site 2121, 000-000-0000
- Completed
Local Institution - 2112
Cleveland, Ohio, 44195
- Recruiting
The University of Texas Southwestern Medical Center - Harold C Simmons Comprehensive Cancer Center
Dallas, Texas, 75390
Tanya Carens Watt, Site 2101
- Completed
Local Institution - 2114
Hershey, Pennsylvania, 17033
- Recruiting
Baylor College of Medicine
Houston, Texas, 77030
Matthew McEvoy, Site 2118
- Completed
Local Institution - 2104
Houston, Texas, 77030
- Recruiting
Children's Hospital Los Angeles
Los Angeles, California, 90027-6062
Leo Mascarenhas, Site 2111, 323-361-5418
- Recruiting
University of California at Los Angeles
Los Angeles, California, 90095
Noah Federman, Site 2109, 310-206-7625
- Recruiting
St. Jude Children's Research Hospital
Memphis, Tennessee, 38015
Alberto Pappo, Site 2103, 901-595-3300
- Completed
Local Institution - 2110
New Brunswick, New Jersey, 08901
- Completed
Local Institution - 2102
New York, New York, 10065
- Completed
Local Institution - 2105
Orlando, Florida, 32806
- Completed
Local Institution - 2120
Orlando, Florida, 32827
- Recruiting
Children's Hospital of Philadelphia-Center for Childhood Cancer Research
Philadelphia, Pennsylvania, 19104
Theodore Laetsch, Site 2117, 267-425-5544
- Withdrawn
Children's Hospital of Richmond at VCU
Richmond, Virginia, 23219
- Recruiting
Maine Medical Center
Scarborough, Maine, 04074
Stanley Chaleff, Site 2115, 207-396-7565
- Recruiting
Washington University School of Medicine in St. Louis
St Louis, Missouri, 63110
Andrew Cluster, Site 2113, 443-745-4180
Spain11 sites, 11 recruiting
- Not yet recruiting
Local Institution - 6105
Barcelona, 08014
Site 6105
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, 8035
Maria Paula Perez Albert, Site 4103
- Recruiting
Hospital Sant Joan De Deu
Esplugues de Llobregat, Barcelona, 08950
Alicia Castaneda Heredia, Site 4106, 34932532100
- Recruiting
Hospital Infantil Universitario Nino Jesus
Madrid, 28009
Alvaro Lassaletta, Site 4105, +34915035938
- Not yet recruiting
Local Institution - 6106
Madrid, 28009
Site 6106
- Recruiting
Clinica Universidad de Navarra
Madrid, 28022
Elena Panizo Morgado, Site 4101, 34913531920
- Recruiting
HM Sanchinarro University Hospital
Madrid, 28050
Marta Osuna Marco, Site 4104, 34917089935
- Recruiting
Clínica Universidad de navarra
Pamplona, Navarre, 31008
Elena Panizo Morgado, Site 4102, 34913531920
- Recruiting
Hospital Universitario Virgen del Rocio
Seville, 41013
Jose Luis Moreno, Site 4108, 955012000
- Recruiting
Hospital Universitario Y Politecnico La Fe
Valencia, 46026
Antonio Juan Ribelles, Site 4107, 961244190
- Not yet recruiting
Local Institution - 6107
Valencia, 46026
Site 6107
France10 sites, 10 recruiting
- Recruiting
Centre Hospitalier Universitaire D'Angers
Angers, 49933
Emilie De Carli, Site 4203, 0241353863
- Recruiting
Centre Hospitalier Universitaire de Bordeaux - Groupe Hospitalier Pellegrin
Bordeaux, 33076
Stephane Ducassou, Site 4201, 0557820438
- Not yet recruiting
Local Institution - 6111
Lyon, Rhone, 69008
Site 6111
- Recruiting
Institut d Hematologie et d Oncologie Pediatriques
Lyon, 69373
Nadege Corradini, Site 4204, 33478782642
- Recruiting
Hôpitaux Universitaires de Marseille Timone
Marseille, 13385
Nicolas Andre, Site 4205, 33491386821
- Not yet recruiting
Local Institution - 6110
Marseille, 13385
Site 6110
- Not yet recruiting
Local Institution - 6112
Nantes, 44093
Site 6112
- Not yet recruiting
Local Institution - 6109
Paris, 75005
Site 6109
- Recruiting
Institut Gustave-Roussy
Villejuif, 94805
Samuel Abbou, Site 4202, 142114211
- Not yet recruiting
Local Institution - 6108
Villejuif, 94805
Site 6108
United Kingdom6 sites, 5 recruiting
- Completed
Local Institution - 4403
Birmingham, B4 6DH
- Recruiting
University Hospital of Wales
Cardiff, CF14 4XW
Madeleine Adams, Site 4401, 02920742107
- Recruiting
Royal Hosp. for Children
Glasgow, G51 4TF
Milind Ronghe, Site 4406
- Recruiting
Alder Hey Children's NHS Foundation Trust
Liverpool, England, L12 2AP
Lisa Howell, Site 4404, +441512933679
- Recruiting
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
Linley Marchall, Site 4405, 209156161
- Recruiting
Great Ormond Street Hospital For Children NHS Foundation Trust
London, WC1N 3JH
Elwira Szychot, Site 4402, 447849760509
Australia4 sites, 3 recruiting
- Recruiting
Perth Childrens Hospital
Nedlands, Western Australia, 6009
Nick Gottardo, Site 6101
- Recruiting
Local Institution - 6104
Randwick, New South Wales, 2031
Site 6104
- Recruiting
Children's Health Queensland Hospital and Health Service
South Brisbane, Queensland, 4101
Timothy Hassall, Site 6102, 61730681111
- Completed
Local Institution - 6103
Westmead, New South Wales, 0
Canada4 sites, 4 recruiting
- Recruiting
University Of Calgary
Calgary, Alberta, T3B 6A8
Victor Lewis, Site 2202, 14039557203
- Recruiting
Stollery Children'S Hospital
Edmonton, Alberta, T6G 2B7
Sunil desai, Site 2201, 17802485415
- Recruiting
St Justine Hospital
Montreal, Quebec, H3T 1C5
Sebastien Perreault, Site 2205, 4384958893
- Recruiting
Children'S Hospital Of Eastern Ontario
Ottawa, Ontario, K1H 8L1
Lesleigh Abbott, Site 2203, 61373776002370
Italy4 sites, 2 recruiting
- Recruiting
Fondazione IRCCS - Istituto Nazionale dei Tumori
Milan, 20133
Michela Casanova, Site 4301, 390223902593
- Withdrawn
Local Institution - 6113
Padova, 35128
- Not yet recruiting
Local Institution - 4302
Rome, 00165
Site 4302
- Withdrawn
Local Institution - 6114
Torino, 10126
South Korea4 sites, 2 recruiting
- Completed
Local Institution - 6303
Seoul, Seodaemun-gu, 03722
- Recruiting
Seoul National University Hospital
Seoul, 03080
Hyoung Jin Kang, Site 6301, 82220723304
- Recruiting
Asan Medical Center
Seoul, 05505
Kyung Nam Koh, Site 6302, +82230105994
- Completed
Local Institution - 6304
Seoul, 06351
Singapore2 sites, 2 recruiting
- Recruiting
National University Hospital
Singapore, 119228
Allen Yeoh, Site 6401, 67724406
- Recruiting
KK Women's and Children's Hospital
Singapore, 229899
Shui Yen Soh, Site 6402, 6563941045
Taiwan2 sites, 1 recruiting
- Completed
Local Institution - 6202
Taipei, 100225
- Recruiting
Taipei Medical University Hospital
Taipei, 11031
Yen-Lin Liu, Site 6201, 886970749572
Denmark1 site, 1 recruiting
- Recruiting
Rigshospitalet - Glostrup
Copenhagen, 2100
Karsten Nysom, Site 4901, 4535450809
About this study
Official title: 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, or NTRK1-3 Alterations (CARE)
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.
Read the 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 15 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 23 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.
- Being tested
- Oral repotrectinib (TPX-0005)
- Keywords
- ALK, ROS1, NTRK1-3, Primary CNS tumor, anaplastic large cell lymphoma, metastatic solid tumor, advanced solid tumor, sarcoma, infantile fibrosarcoma, glioblastoma, soft tissue schwannoma, solitary fibrous tumor, glioma, inflammatory myofibroblastic tumor, pediatric
- Medical subject headings
- Lymphoma, Lymphoma, Large-Cell, Anaplastic, Neoplasm Metastasis, Sarcoma, Glioblastoma, Solitary Fibrous Tumors, Glioma, Granuloma, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral repotrectinib (TPX-0005)Drug
Also called Oral repotrectinib (TPX-0005) capsules, Oral repotrectinib (TPX-0005) oral suspension, repotrectinib
Oral repotrectinib (TPX-0005)
| Study group | Role | What they receive |
|---|---|---|
| Repotrectinib (TPX-0005) | Experimental | 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 Receives: Drug: Oral repotrectinib (TPX-0005) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities (DLTs) (Phase 1)
Define the dose limiting toxicities (DLTs) (Phase 1)
Measured: Within 28 days of the first repotrectinib dose
Pediatric Recommended Phase 2 Dose (RP2D) (Phase 1)
To determine the pediatric RP2D (Phase 1)
Measured: Within 28 days of the last patient dosed in escalation
Overall Response Rate (ORR) (Phase 2)
To determine the confirmed ORR of repotrectinib (TPX-0005) as assessed by Blinded Independent Central Review (Phase 2)
Measured: Two to three years after first dose of repotrectinib
Secondary outcomes (12)
Overall Response Rate (ORR) (Phase 1)
To determine the overall response rate (ORR) by Blinded Independent Central Review (BICR) (Phase 1)
Measured: Approximately three years
Clinical Benefit Rate (CBR) (Phase 1 and Phase 2)
To determine the CBR of repotrectinib (TPX-0005) (Phase 1 and Phase 2)
Measured: Approximately three years
Time to response (TTR) (Phase 1 and Phase 2)
To determine the TTR of reprotrectinib (TPX-005) (Phase 1 and Phase 2)
Measured: Approximately three years
Duration of response (DOR) (Phase 1 and Phase 2)
To determine the DOR of repotrectinib (TPX-0005) (Phase 1 and Phase 2)
Measured: Approximately three years
Intracranial objective response rate (IC-ORR) (Phase 1 and Phase 2)
To determine the IC-ORR of repotrectinib in subjects with measurable brain metastases (TPX-005) (Phase 1 and Phase 2)
Measured: Approximately three years
Central Nervous System Progression-Free Survival (CNS-PFS) (Phase 2)
CNS-PFS in subjects with measurable brain metastases (Phase 2)
Measured: Approximately three years
Progression-free survival (PFS) (Phase 2)
To determine the PFS (Phase 2)
Measured: Approximately three years
Overall survival (OS) (Phase 2)
To determine the OS (Phase 2)
Measured: Approximately three years
Maximum concentration of repotrectinib in plasma (Cmax)
To determine the Cmax
Measured: 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)
To determine the AUC
Measured: Pre-dose and up to 24 hours post-dose on Day 1 and Day 15 in Cycle 1 (each cycle is 28 days)
Number of participants with laboratory abnormalities
Measured: Approximately three years
Number of Participants with Adverse events
Measured: Approximately three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2019
- Study start12 Mar 2020
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Turning Point Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04094610
- Sponsor's protocol ID
- CA127-1029
- Other IDs
- CA127-1029, TPX-0005-07, 2023-506464-14, 2023
- Status last verified
- Sep 2026
- First submitted
- 12 Sep 2019
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
- Expanded access
- Available
Publications
Wachter F, Al-Ibraheemi A, Trissal MC, Hollowell M, DuBois SG, Collins NB, Church AJ, Janeway KA. Molecular Characterization of Inflammatory Tumors Facilitates Initiation of Effective Therapy. Pediatrics. 2021 Dec 1;148(6):e2021050990. doi: 10.1542/peds.2021-050990.
PubMed 34814185
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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, or NTRK1-3 Alterations (CARE)
- ClinicalTrials.gov ID
- NCT04094610
- Acronym / sponsor ID
- CA127-1029
- Keywords
- ALK, ROS1, NTRK1-3, Primary CNS tumor, anaplastic large cell lymphoma, metastatic solid tumor, advanced solid tumor, sarcoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Turning Point Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 12 Mar 2020 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 19 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 15 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 23 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Repotrectinib (TPX-0005) | Experimental | Drug: Oral 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 |
Who may qualify
- Ages
- Up to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- 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.
- 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.
Key exclusion criteria (11 listed)
- 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.
- Any of the following cardiac criteria:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral repotrectinib (TPX-0005)Also: Oral repotrectinib (TPX-0005) capsules, Oral repotrectinib (TPX-0005) oral suspension, repotrectinibOral repotrectinib (TPX-0005) | Drug | Repotrectinib (TPX-0005) |
Primary outcome
Dose limiting toxicities (DLTs) (Phase 1)
Time frame: Within 28 days of the first repotrectinib dose
Define the dose limiting toxicities (DLTs) (Phase 1)
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)
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)
12 secondary outcomes
Overall Response Rate (ORR) (Phase 1)
Time frame: Approximately three years
Clinical Benefit Rate (CBR) (Phase 1 and Phase 2)
Time frame: Approximately three years
Time to response (TTR) (Phase 1 and Phase 2)
Time frame: Approximately three years
Duration of response (DOR) (Phase 1 and Phase 2)
Time frame: Approximately three years
Intracranial objective response rate (IC-ORR) (Phase 1 and Phase 2)
Time frame: Approximately three years
Central Nervous System Progression-Free Survival (CNS-PFS) (Phase 2)
Time frame: Approximately three years
Progression-free survival (PFS) (Phase 2)
Time frame: Approximately three years
Overall survival (OS) (Phase 2)
Time frame: 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)
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)
Number of participants with laboratory abnormalities
Time frame: Approximately three years
Number of Participants with Adverse events
Time frame: Approximately three years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- Derived from this study: PubMed 34814185Wachter F, Al-Ibraheemi A, Trissal MC, Hollowell M, DuBois SG, Collins NB, Church AJ, Janeway KA. Molecular Characterization of Inflammatory Tumors Facilitates Initiation of Effective Therapy. Pediatrics. 2021 Dec 1;148(6):e2021050990. doi: 10.1542/peds.2021-050990.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
BMS Clinical Trials Contact Center www.BMSClinicalTrials.com contact
First line of the email MUST contain NCT # and Site #. contact
Bristol-Myers Squibb study director
Bristol-Myers Squibb
68 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Oral repotrectinib (TPX-0005) in people with Locally Advanced Solid Tumors and Metastatic Solid Tumors, run by Turning Point Therapeutics, Inc. at 68 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 68 sites in United States, Spain, France, United Kingdom, Australia and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact BMS Clinical Trials Contact Center www.BMSClinicalTrials.com (855-907-3286, Clinical.Trials@bms.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicities (DLTs) (Phase 1) (time frame: Within 28 days of the first repotrectinib dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04094610, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.