NTRK fusion cancers previously treated with a TRK inhibitor MedDRA version: 21.0 Level: LLT Classification code 10049516 Term: Malignant tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10007958 Term: Central nervous system neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Selitrectinib
Product Code: BAY 2731954
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not available
CAS Number: 2097002-61-2
Current Sponsor code: BAY 2731954
Other descripti
Sponsors
Bayer Consumer Care AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures. Parent/guardian of child or adolescent subjects has the ability to understand, agree to, and sign the study Informed Consent Form and applicable Pediatric Assent Form before initiation of any protocol related procedures; subject has the ability to give assent, as applicable, at the time of parental/guardian consent. 2. Advanced solid tumor for which, in the opinion of the Investigator, no other standard therapy offers greater benefit. 3. A solid tumor diagnosis in the setting of: a. a documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitor b. a documented NTRK fusion unresponsive to a prior TRK inhibitor c. a documented NTRK fusion and a clinical history of intolerance to a prior TRK inhibitor. A list of agents with known TRK inhibitor activity is provided in appendix A. Other agents not listed may also be considered upon Sponsor review. NTRK (NTRK1, NTRK2, and NTRK3) gene fusions will be identified in a CLIA-certified (or equivalently-accredited diagnostic) laboratory. If such a report cannot be provided, other available certifications/accreditations are required and need to be documented. Acceptable methods of detection of NTRK fusion include next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (RT-PCR) with the following documented in a written report: • For NGS, the report indicates that a fusion was detected between an NTRK gene (NTRK1, NTRK2, or NTRK3) and a specific partner gene. • For FISH, the report indicates that a probe mapping to an NTRK gene (NTRK1, NTRK2, or NTRK3) and/or a probe mapping to a specific partner gene were found to be colocalized by microscopy. • For RT-PCR, the report indicates that a pair of primers targeting an NTRK gene (NTRK1, NTRK2, or NTRK3) on one end and a specific partner gene on the other end amplified a detectable target. If enrolling a patient based on the pan-TRK IHC result, documentation of NTRK fusion must be provided using NGS. If enrolling a patient based on FISH result, additional documentation of NTRK fusion using NGS is preferred. Exception: Patients with infantile fibrosarcoma (IFS) or congenital mesoblastic nephroma (CMN) may be enrolled based on confirmation of an ETV6 aberration without an identified partner gene (for example, patients may have been diagnosed with IFS or CMN based on an ETV6+ FISH test without identifying [or testing] for NTRK3). 4. Performance Status: Eastern Cooperative Oncology Group (ECOG) score = 2 (in adults), Karnofsky Performance Status (KPS) = 50% (age = 16 years) or Lansky Performance Score (LPS) = 50% (age < 16years). 5. Evaluable and/or measurable disease by RECIST v1.1, RANO or International Neuroblastoma Response Criteria INRC. 6. Life expectancy of at least 3 months. 7. At least 1 month of age. 8. Tissue submission. Samples from 2 time points are required if available. a. Tumor sample obtained after patient progression on therapy with last kinase inhibitor with anti TRK activity prior to consenting for this trial. A fresh biopsy in this setting is preferred if it can be safely obtained or this may be an archived sample. See Section 7.6.3 for specifics. b. Archived tumor tissue sample obtained prior to when patient started on the first anti-TRK therapy. If the site has tissue from both
Exclusion criteria
Exclusion criteria: 1. Prior exposure to second generation TRK inhibitor (e.g. selitrectinib, repotrectinib (TPX-0005), taletrectinib (DS-6501b/AB-106)). Exception is in case patient presented intolerance to the second generation TRK inhibitor agent and the duration of exposure was less than 28 days. No previous treatment with selitrectinib is allowed. 2. If received recent therapy, evidence of moderate-severe/uncontrolled toxicities that in the opinion of the investigator are limiting of subsequent therapy or unstable organ dysfunction due to previous treatment. 3. Concurrent treatment with a strong CYP3A4 inhibitor or inducer (refer to Appendix B), consumption of grapefruit juice or Seville orange, or drugs associated with QT prolongation. The Investigator should review concomitant medications with their site pharmacist as the list can change frequently. 4. Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of selitrectinib, cardiomyopathy; current or known history within the past 6 months of prolonged QT interval corrected for heart rate (QTc interval) > 480 milliseconds. If there is a known explanation for a limited period of a prolonged QT interval (i.e., a medication known to cause prolonged QT interval was administered and has since been discontinued with clearly documented normal QT interval thereafter), that subject may be enrolled. If subject suffers from congestive heart failure, with onset more than 3 months prior to planned start of selitrectinib, then New York Heart Association (NYHA) classification should be functional capacity I at maximum (Appendix J). 5. Major surgery within 7 days of enrollment. Catheter placement, endoscopic procedures, and dental surgery are not considered major surgery. 6. Uncontrolled systemic bacterial, fungal or viral infection. Infections treated with a stable dose of antimicrobial therapy for at least 7 days are allowed. Prophylactic antibiotics are allowed. 7. Pregnancy or lactation. 8. Known hypersensitivity to any of the components of the investigational agent, selitrectinib or Ora Sweet® SF and OraPlus®, for patients who will take the selitrectinib suspension. Please refer to Appendix G for the complete list of ingredients for Ora-Sweet® SF and Ora-Plus®. 9. Known history of human immunodeficiency virus (HIV). Refer to Section 4.2 Exclusion Criteria of the protocol for additional details. 10. Hepatitis B (HBV) or C (HCV) infection. Refer to Section 4.2 Exclusion Criteria of the protocol for additional details. 11. Any malabsorption condition. 12. Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the recommended dose for further study of oral selitrectinib in 2 patient groups with previously treated neurotrophic tyrosine receptor kinase (NTRK) fusion cancers defined as age 12 years and older and age < 12 years. ;Secondary Objective: • To characterize the pharmacokinetic (PK) properties of selitrectinib • To characterize the safety and tolerability of selitrectinib. • To assess objective response rate (ORR) according to best response by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as determined by Investigator. • To assess the ORR according to best response by Response Assessment in Neuro Oncology (RANO), as determined by Investigator, in patients with primary central nervous system (CNS) malignancies with NTRK fusion. ;Primary end point(s): MTD and/or recommended dose for further study of selitrectinib in patients age 12 years and older and age < 12 years. ;Timepoint(s) of evaluation of this end point: Every cohort from baseline until disease progression, unacceptable toxicity, patient's withdrawal of consent, or death. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Incidence, severity, and duration of AEs, including all, serious, and those considered treatment related. • Changes from baseline in clinical safety laboratory values and vital signs. • ORR as determined by the Investigator, in patients with a documented NTRK fusion cancer previously treated with a TRK inhibitor using RECIST 1.1 for solid tumors. • ORR as determined by the treating Investigator using RANO in patients with primary CNS malignancies,. • To characterize the PK properties of selitrectinib (Cmax, AUC(0-10), AUC(0-12) for BID dosing and AUC(0-24) for QD dosing, if applicable. ;Timepoint(s) of evaluation of this end point: Phase 1: PK properties of selitrectinib will be determined between C1D6 and C1D8 Phase 1 and Phase 2: EORTC QLQ-C30 and EQ-5D or PedsQL should be conducted at the same cycle visits as the disease assessment. | — |
Countries
Australia, Belgium, Denmark, France, Germany, Hong Kong, Ireland, Italy, Korea, Republic of, Singapore, Spain, United Kingdom, United States
Contacts
Public ContactBayer Clinical Trials Contact
Bayer AG
Outcome results
None listed