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A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
NCT04094610 · Turning Point Therapeutics, Inc.
In plain English
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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, NTRK1-3 Alterations
About this study
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.
Eligibility 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.
Study design
Enrollment target: 75 participants
Allocation: na
Masking: none
Age groups: child, adult
Timeline
Starts: 2020-03-12
Estimated completion: 2027-09-30
Last updated: 2025-11-19
Interventions
Drug: Oral repotrectinib (TPX-0005)
Primary outcomes
- • Dose limiting toxicities (DLTs) (Phase 1) (Within 28 days of the first repotrectinib dose)
- • Pediatric Recommended Phase 2 Dose (RP2D) (Phase 1) (Within 28 days of the last patient dosed in escalation)
- • Overall Response Rate (ORR) (Phase 2) (Two to three years after first dose of repotrectinib)
Sponsor
Turning Point Therapeutics, Inc. · industry
Contacts & investigators
ContactBMS Study Connect Contact Center www.BMSStudyConnect.com · contact · Clinical.Trials@bms.com · 855-907-3286
ContactFirst line of the email MUST contain the NCT# and Site #. · contact
InvestigatorBristol-Myers Squibb · study_director, Bristol-Myers Squibb
All locations (68)
Children's Hospital Los AngelesRecruiting
Los Angeles, California, United States
University of California at Los AngelesRecruiting
Los Angeles, California, United States
Children's Hospital Colorado - Anschutz Medical CampusRecruiting
Aurora, Colorado, United States
Local Institution - 2105Completed
Orlando, Florida, United States
Local Institution - 2120Completed
Orlando, Florida, United States
Children's Healthcare of Atlanta - Egleston HospitalRecruiting
Atlanta, Georgia, United States
Maine Medical CenterRecruiting
Scarborough, Maine, United States
Dana Farber Cancer Institute.Recruiting
Boston, Massachusetts, United States
Washington University School of Medicine in St. LouisRecruiting
St Louis, Missouri, United States
Local Institution - 2110Completed
New Brunswick, New Jersey, United States
Local Institution - 2102Completed
New York, New York, United States
Levine Children's Hospital- Pediatric Neuro-OncologyRecruiting
Charlotte, North Carolina, United States
Local Institution - 2112Completed
Cleveland, Ohio, United States
Local Institution - 2114Completed
Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia-Center for Childhood Cancer ResearchRecruiting
Philadelphia, Pennsylvania, United States
St. Jude Children's Research HospitalRecruiting
Memphis, Tennessee, United States
The University of Texas Southwestern Medical Center - Harold C Simmons Comprehensive Cancer CenterRecruiting
Dallas, Texas, United States
Baylor College of MedicineRecruiting
Houston, Texas, United States
Local Institution - 2104Completed
Houston, Texas, United States
Children's Hospital of Richmond at VCUWithdrawn
Richmond, Virginia, United States
Local Institution - 6104Recruiting
Randwick, New South Wales, Australia
Local Institution - 6103Completed
Westmead, New South Wales, Australia
Children's Health Queensland Hospital and Health ServiceRecruiting
South Brisbane, Queensland, Australia
Perth Childrens HospitalRecruiting
Nedlands, Western Australia, Australia
University Of CalgaryRecruiting
Calgary, Alberta, Canada
Stollery Children'S HospitalRecruiting
Edmonton, Alberta, Canada
Children'S Hospital Of Eastern OntarioRecruiting
Ottawa, Ontario, Canada
St Justine HospitalRecruiting
Montreal, Quebec, Canada
Rigshospitalet - GlostrupRecruiting
Copenhagen, Denmark
Local Institution - 6111Not Yet Recruiting
Lyon, Rhone, France
Centre Hospitalier Universitaire D'AngersRecruiting
Angers, France
Centre Hospitalier Universitaire de Bordeaux - Groupe Hospitalier PellegrinRecruiting
Bordeaux, France
Institut d Hematologie et d Oncologie PediatriquesRecruiting
Lyon, France
Hôpitaux Universitaires de Marseille TimoneRecruiting
Marseille, France
Local Institution - 6110Not Yet Recruiting
Marseille, France
Local Institution - 6112Not Yet Recruiting
Nantes, France
Local Institution - 6109Not Yet Recruiting
Paris, France
Institut Gustave-RoussyRecruiting
Villejuif, France
Local Institution - 6108Not Yet Recruiting
Villejuif, France
Fondazione IRCCS - Istituto Nazionale dei TumoriRecruiting
Milan, Italy
Local Institution - 6113Withdrawn
Padova, Italy
Local Institution - 4302Not Yet Recruiting
Rome, Italy
Local Institution - 6114Withdrawn
Torino, Italy
National University HospitalRecruiting
Singapore, Singapore
KK Women's and Children's HospitalRecruiting
Singapore, Singapore
Local Institution - 6303Completed
Seoul, Seodaemun-gu, South Korea
Seoul National University HospitalRecruiting
Seoul, South Korea
Asan Medical CenterRecruiting
Seoul, South Korea
Local Institution - 6304Completed
Seoul, South Korea
Hospital Sant Joan De DeuRecruiting
Esplugues de Llobregat, Barcelona, Spain
Clínica Universidad de navarraRecruiting
Pamplona, Navarre, Spain
Local Institution - 6105Not Yet Recruiting
Barcelona, Spain
Hospital Universitari Vall d'HebronRecruiting
Barcelona, Spain
Hospital Infantil Universitario Nino JesusRecruiting
Madrid, Spain
Local Institution - 6106Not Yet Recruiting
Madrid, Spain
Clinica Universidad de NavarraRecruiting
Madrid, Spain
HM Sanchinarro University HospitalRecruiting
Madrid, Spain
Hospital Universitario Virgen del RocioRecruiting
Seville, Spain
Hospital Universitario Y Politecnico La FeRecruiting
Valencia, Spain
Local Institution - 6107Not Yet Recruiting
Valencia, Spain
National Taiwan University HospitalRecruiting
Taipei, Taiwan
Taipei Medical University HospitalRecruiting
Taipei, Taiwan
Alder Hey Children's NHS Foundation TrustRecruiting
Liverpool, England, United Kingdom
Local Institution - 4403Completed
Birmingham, United Kingdom
University Hospital of WalesRecruiting
Cardiff, United Kingdom
Royal Hosp. for ChildrenRecruiting
Glasgow, United Kingdom
The Royal Marsden NHS Foundation TrustRecruiting
London, United Kingdom
Great Ormond Street Hospital For Children NHS Foundation TrustRecruiting
London, United Kingdom