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

NCT04094610 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: CA127-1029TPX-0005-07
• Study Type: interventional
• Target: 75
• Locations: 11 countries
• Sites: 68

Brief 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 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.

Conditions

Locally Advanced Solid Tumors; Metastatic Solid Tumors; Lymphoma; Primary CNS Tumors

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

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicities (DLTs) (Phase 1)

  Define the dose limiting toxicities (DLTs) (Phase 1)

  Within 28 days of the first repotrectinib dose

• Pediatric Recommended Phase 2 Dose (RP2D) (Phase 1)

  To determine the pediatric RP2D (Phase 1)

  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)

  Two to three years after first dose of repotrectinib

Secondary Outcomes (10)

• Overall Response Rate (ORR) (Phase 1)

  Approximately three years

• Clinical Benefit Rate (CBR) (Phase 1 and Phase 2)

  Approximately three years

• Time to response (TTR) (Phase 1 and Phase 2)

  Approximately three years

• Duration of response (DOR) (Phase 1 and Phase 2)

  Approximately three years

• Intracranial objective response rate (IC-ORR) (Phase 1 and Phase 2)

  Approximately three years

Study Arms (1)

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

Drug: Oral repotrectinib (TPX-0005)

Interventions

Oral repotrectinib (TPX-0005) DRUG

Oral repotrectinib (TPX-0005)

Also known as: Oral repotrectinib (TPX-0005) capsules, Oral repotrectinib (TPX-0005) oral suspension, repotrectinib

Repotrectinib (TPX-0005)

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Turning Point Therapeutics, Inc.: lead

Study Sites (68)

Children's Hospital Los Angeles

Los Angeles, California, 90027-6062, United States

RECRUITING

University of California at Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Children's Hospital Colorado - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Local Institution - 2105

Orlando, Florida, 32806, United States

COMPLETED

Local Institution - 2120

Orlando, Florida, 32827, United States

COMPLETED

Children's Healthcare of Atlanta - Egleston Hospital

Atlanta, Georgia, 30329, United States

RECRUITING

Maine Medical Center

Scarborough, Maine, 04074, United States

RECRUITING

Dana Farber Cancer Institute.

Boston, Massachusetts, 02215, United States

RECRUITING

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

Local Institution - 2110

New Brunswick, New Jersey, 08901, United States

COMPLETED

Local Institution - 2102

New York, New York, 10065, United States

COMPLETED

Levine Children's Hospital- Pediatric Neuro-Oncology

Charlotte, North Carolina, 28203, United States

RECRUITING

Local Institution - 2112

Cleveland, Ohio, 44195, United States

COMPLETED

Local Institution - 2114

Hershey, Pennsylvania, 17033, United States

COMPLETED

Children's Hospital of Philadelphia-Center for Childhood Cancer Research

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 38015, United States

RECRUITING

The University of Texas Southwestern Medical Center - Harold C Simmons Comprehensive Cancer Center

Dallas, Texas, 75390, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

Local Institution - 2104

Houston, Texas, 77030, United States

COMPLETED

Children's Hospital of Richmond at VCU

Richmond, Virginia, 23219, United States

WITHDRAWN

Local Institution - 6104

Randwick, New South Wales, 2031, Australia

RECRUITING

Local Institution - 6103

Westmead, New South Wales, 0, Australia

COMPLETED

Children's Health Queensland Hospital and Health Service

South Brisbane, Queensland, 4101, Australia

RECRUITING

Perth Childrens Hospital

Nedlands, Western Australia, 6009, Australia

RECRUITING

University Of Calgary

Calgary, Alberta, T3B 6A8, Canada

RECRUITING

Stollery Children'S Hospital

Edmonton, Alberta, T6G 2B7, Canada

RECRUITING

Children'S Hospital Of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

RECRUITING

St Justine Hospital

Montreal, Quebec, H3T 1C5, Canada

RECRUITING

Rigshospitalet - Glostrup

Copenhagen, 2100, Denmark

RECRUITING

Local Institution - 6111

Lyon, Rhone, 69008, France

NOT YET RECRUITING

Centre Hospitalier Universitaire D'Angers

Angers, 49933, France

RECRUITING

Centre Hospitalier Universitaire de Bordeaux - Groupe Hospitalier Pellegrin

Bordeaux, 33076, France

RECRUITING

Institut d Hematologie et d Oncologie Pediatriques

Lyon, 69373, France

RECRUITING

Hôpitaux Universitaires de Marseille Timone

Marseille, 13385, France

RECRUITING

Local Institution - 6110

Marseille, 13385, France

NOT YET RECRUITING

Local Institution - 6112

Nantes, 44093, France

NOT YET RECRUITING

Local Institution - 6109

Paris, 75005, France

NOT YET RECRUITING

Institut Gustave-Roussy

Villejuif, 94805, France

RECRUITING

Local Institution - 6108

Villejuif, 94805, France

NOT YET RECRUITING

Fondazione IRCCS - Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Local Institution - 6113

Padua, 35128, Italy

WITHDRAWN

Local Institution - 4302

Rome, 00165, Italy

NOT YET RECRUITING

Local Institution - 6114

Torino, 10126, Italy

WITHDRAWN

National University Hospital

Singapore, 119228, Singapore

RECRUITING

KK Women's and Children's Hospital

Singapore, 229899, Singapore

RECRUITING

Local Institution - 6303

Seoul, Seodaemun-gu, 03722, South Korea

COMPLETED

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Local Institution - 6304

Seoul, 06351, South Korea

COMPLETED

Hospital Sant Joan De Deu

Esplugues de Llobregat, Barcelona, 08950, Spain

RECRUITING

Clínica Universidad de navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

Local Institution - 6105

Barcelona, 08014, Spain

NOT YET RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

RECRUITING

Hospital Infantil Universitario Nino Jesus

Madrid, 28009, Spain

RECRUITING

Local Institution - 6106

Madrid, 28009, Spain

NOT YET RECRUITING

Clinica Universidad de Navarra

Madrid, 28022, Spain

RECRUITING

HM Sanchinarro University Hospital

Madrid, 28050, Spain

RECRUITING

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

RECRUITING

Hospital Universitario Y Politecnico La Fe

Valencia, 46026, Spain

RECRUITING

Local Institution - 6107

Valencia, 46026, Spain

NOT YET RECRUITING

National Taiwan University Hospital

Taipei, 100225, Taiwan

RECRUITING

Taipei Medical University Hospital

Taipei, 11031, Taiwan

RECRUITING

Alder Hey Children's NHS Foundation Trust

Liverpool, England, L12 2AP, United Kingdom

RECRUITING

Local Institution - 4403

Birmingham, B4 6DH, United Kingdom

COMPLETED

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

RECRUITING

Royal Hosp. for Children

Glasgow, G51 4TF, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

RECRUITING

Great Ormond Street Hospital For Children NHS Foundation Trust

London, WC1N 3JH, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 34814185 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large-Cell, Anaplastic; Neoplasm Metastasis; Sarcoma; Glioblastoma; Solitary Fibrous Tumors; Glioma; Granuloma, Plasma Cell

Interventions

repotrectinib; Capsules; Suspensions

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Connective and Soft Tissue; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Granuloma

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Colloids; Complex Mixtures

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Central Study Contacts

BMS Study Connect Contact Center www.BMSStudyConnect.com

CONTACT

855-907-3286; Clinical.Trials@bms.com

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

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 12, 2019
• First Posted: September 19, 2019
• Study Start: March 12, 2020
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); FR (10); ES (11); IT (4); KR (4); TW (2); GB (6); CA (4); DK (1); SG (2); US (20)