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

  • STATUS
    Recruiting
  • End date
    Dec 3, 2023
  • participants needed
    75
  • sponsor
    Turning Point Therapeutics, Inc.
Updated on 3 February 2021
cancer
tyrosine
lymphoma
measurable disease
ROS1
chemotherapy regimen
solid tumour

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 subjects with advanced or metastatic malignancies harboring ALK, ROS1, or NTRK1-3 alterations.

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)-nave, 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.

Details
Condition Lymphoma, Lymphoproliferative Disorder, Lymphoma, Non-Hodgkin's Lymphoma, Locally Advanced Solid Tumors, Metastatic Solid Tumors, Lymphoproliferative disorders, Primary CNS Tumors, lymphomas
Treatment Oral repotrectinib (TPX-0005)
Clinical Study IdentifierNCT04094610
SponsorTurning Point Therapeutics, Inc.
Last Modified on3 February 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age less than or equal to 25 yrs?
Gender: Male or Female
Do you have any of these conditions: Locally Advanced Solid Tumors or Metastatic Solid Tumors or Lymphoproliferative Disorder or Lymphoma or Primary CNS Tumors or Lymphoproliferative diso...?
Do you have any of these conditions: lymphomas or Lymphoma or Lymphoproliferative disorders or Primary CNS Tumors or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma or Locally Advanced ...?
Do you have any of these conditions: Metastatic Solid Tumors or Locally Advanced Solid Tumors or Lymphoma or Primary CNS Tumors or Lymphoproliferative disorders or lymphomas or Non-Hodgki...?
Do you have any of these conditions: Primary CNS Tumors or Lymphoproliferative disorders or Lymphoma or lymphomas or Locally Advanced Solid Tumors or Non-Hodgkin's Lymphoma or Lymphoproli...?
Do you have any of these conditions: Metastatic Solid Tumors or Lymphoma or Primary CNS Tumors or Lymphoproliferative Disorder or Lymphoproliferative disorders or Non-Hodgkin's Lymphoma o...?
Do you have any of these conditions: lymphomas or Lymphoproliferative disorders or Lymphoma or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma or Primary CNS Tumors or Locally Advanced ...?
Documented genetic ALK, ROS1, or NTRK1-3 alteration (point mutation, fusion, amplification) 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
Age <12 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 Criteria (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 14 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
Adequate hematologic, renal and hepatic function
Phase 2 Inclusion Criteria
Age 12 to <25 years
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 nave
Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated
Cohort 3: subjects with tumors or ALCL characterized by other ALK/ROS1/NTRK alterations or NTRK fusions without centrally confirmed measurable disease or not otherwise eligible for Cohort 1 or 2
Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment

Exclusion Criteria

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 (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) > 470 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
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