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-DE

Lead Sponsor: Bayer Consumer Care AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 186

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 studyspecific
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 < 16
years).
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 7.5.4 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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