Phase 1/2 Open Label solid tumour Safety and Tolerability study in Pediatric and Young Adult subjects.
- Conditions
- Advanced solid tumorsMedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003055-11-DK
- Lead Sponsor
- Turning Point Therapeutics, Inc. (a wholly owned subsidiary of Bristol Myers Squibb Company)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 75
1.Phase 2: EU will not participate in Cohort 1.
Cohort 2: Subjects with NTRK+ advanced solid tumors (including primary CNS tumors), TRK TKI-pretreated. Nonresponse, disease progression or intolerability to at least 1 but no more than 2 prior TRK TKIs. Any prior lines are allowed.
Cohort 3: in the EU: (1) subjects with NTRK fusions without centrally confirmed measurable disease but otherwise eligible for Cohort 2, and (2) subjects with ROS1 fusions.
•Documented genetic ALK, ROS1, or NTRK1-3 alteration as identified by local testing in a CLIA laboratory in the US or equivalent.
•For subjects enrolled per tissue-based test, adequate tumor tissue should be sent prior to enrollment to the central lab. If archived tumor tissue is not available, a fresh biopsy should be obtained.
For subjects enrolled by liquid biopsy test; blood samples should be sent prior to enrollment to the central lab.
2.Subjects must have recovered from the acute toxic effects of all previous therapies prior to study enrollment to CTCAE v4.03 criteria =grade 1, with the exception of alopecia. Subjects must not have received the therapies indicated below for the specified time period:
•Chemotherapy: Last dose given at least 14 days or 5 half-lives before the start date for repotrectinib.
•Monoclonal antibodies (not including IO therapeutic antibodies): Last dose given at least 21 days prior to the start date for repotrectinib.
•Immunotherapy (eg, IO therapeutic antibodies or tumor vaccine): Subject is eligible after 28 days of completion prior to first dose of repotrectinib. Steroids are not considered immunotherapy.
•Radiation therapy: Subjects must not have received radiation for a minimum of 2 weeks prior to study enrollment. If extensive bone marrow radiation, at least 42 days must have elapsed.
•HSCT: Subjects are eligible 12 weeks after infusion following myeloablative therapy (timed from first day of repotrectinib). Subjects who have received an infusion to support nonmyeloablative therapy (such as 131I MIBG) are eligible at any time as long as they meet the other criteria.
•131I-MIBG therapy: A minimum of 6 weeks must have elapsed after 131I-MIBG therapy prior to start of repotrectinib.
•Growth factors: Subjects are eligible 14 days after last dose of long-acting growth factor or 7 days after short-acting growth factor.
•Any investigational agent or anticancer therapy other than chemotherapy and not otherwise noted: Not within 2 weeks prior to planned start of repotrectinib or 5 half-lives, whichever is shorter.
•Any prior treatment with a TKI of ALK/ROS1/NTRK does NOT exclude subject from study.
3.All subjects must have measurable disease by RECIST v1.1 or RANO criteria at time of enrollment.
For Phase 2 subjects in Cohort 2 must have prospectively confirmed measurable disease by BICR prior to enrollment.
•Exception: Neuroblastoma subjects are permitted to have evaluable disease only.
4.Subjects with Primary CNS Tumors or metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 14 days prior to enrollment.
5.Subjects must have a Lansky (<16 years) or Karnofsky (=16 years) score =50. Subjects who are unable to walk because of paralysis or tumor pain, but who are up in a wheelchair, will be considered ambulatory for the performance score.
6.Life expectancy =12 weeks.
7.Screening Local laboratory values:
ANC=1.5 × 109/L, =0.75 × 109L, if known bone marrow involvement
PLT =100 × 109/L independent of platelets tran
1. Concurrent participation in another therapeutic clinical trial.
2. Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
3. Major surgery within 14 days (2 weeks) prior to Cycle 1 Day 1. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
4. Subjects who are pregnant or breast feeding.
5. Subjects with known active infections requiring ongoing treatment (bacterial, fungal, or viral, including HIV).
6. Subjects with gastrointestinal disease (eg, Crohn’s disease, ulcerative colitis, short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
7. Any of the following cardiac criteria:
• Mean resting corrected QT interval (electrocardiogram [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 3 ECGs, using the screening clinic ECG machine-derived QTc value
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (eg, 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, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval (Appendix 5)
8. Subjects with peripheral neuropathy with CTCAE grade = 2.
9. Subjects with other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that, per the judgement of the Investigator or Sponsor, may increase the risk associated with study participation or study drug administration, or that may interfere with the interpretation of study results, or make the subject inappropriate for entry into the study, or could compromise protocol objectives.
10. Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers as listed in Appendix 4.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method