A Phase 1 Study of the TRK Inhibitor Selitrectinib (BAY2731954) in Adult and Pediatric Subjects with Previously Treated NTRK Fusion Cancers

Phase 1

Conditions: TRK fusion cancers previously treated with a TRK inhibitor
MedDRA version: 21.0Level: LLTClassification code 10049516Term: Malignant tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0Level: PTClassification code 10007958Term: Central nervous system neoplasmSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-004246-20-DK

Lead Sponsor: Bayer Consumer Care AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 81

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

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.

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

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