A PHASE 1/2, OPEN-LABEL, DOSE-ESCALATION AND EXPANSION STUDY OF ENTRECTINIB (RXDX-101) IN PEDIATRICS AND YOUNG ADULTS WITH NO CURATIVE FIRST-LINE TREATMENT OPTION OR RECURRENT/REFRACTORY SOLID TUMORS AND PRIMARY CNS TUMORS

NOT ENROLLING
Protocol # :
16-045
Conditions
Solid Tumors
CNS Tumors
Phase
I
Disease Sites
Lip, Oral Cavity and Pharynx
Esophagus
Stomach
Small Intestine
Colon
Rectum
Anus
Liver
Pancreas
Other Digestive Organ
Larynx
Lung
Other Respiratory and Intrathoracic Organs
Bones and Joints
Soft Tissue
Mycosis Fungoides
Other Skin
Breast
Cervix
Corpus Uteri
Ovary
Other Female Genital
Prostate
Other Male Genital
Urinary Bladder
Kidney
Other Urinary
Eye and Orbit
Brain and Nervous System
Thyroid
Unknown Sites
Ill-Defined Sites
Other Endocrine System
Kaposi's Sarcoma
Melanoma, Skin
Principal Investigator
Shusterman, Suzanne

Trial Description

This is an open-label, Phase 1/2 multicenter dose escalation study in pediatric patients with
relapsed or refractory extracranial solid tumors (Phase 1), with additional expansion cohorts
(Phase 2) in patients with primary brain tumors harboring NTRK1/2/3 or ROS1 gene fusions, and
extracranial solid tumors harboring NTRK1/2/3 or ROS1 gene fusions.

Eligibility Requirements

Inclusion Criteria:

1. Disease status:

- Phase 1 portion (closed): Participants must have measurable or evaluable disease,
as defined by RECIST v1.1

- Phase 2 portion:

- Part B: Participants must have measurable or evaluable disease, as defined
by RANO

- Part C (closed): Participants must have measurable or evaluable disease, as
defined by RECIST v1.1 ± Curie Scale

- Part D: Participants must have measurable or evaluable disease, as defined
by RECIST v1.1

- Part E (closed): Participants must have measurable or evaluable disease, as
defined by RECIST v1.1 ± Curie Scale or RANO

2. Tumor type:

- Phase 1 portion:

* Part A: Relapsed or refractory extracranial solid tumors

- Phase 2 portion

- Part B: Primary brain tumors with NTRK1/2/3 or ROS1 gene fusions; gene
fusions are defined as those predicted to translate into a fusion protein
with a functional TRKA/B/C or ROS1 kinase domain, without a concomitant
second oncodriver as determined by a nucleic acid-based diagnostic testing
method

- Part D: Extracranial solid tumors (including NB) with NTRK1/2/3 or ROS1 gene
fusions; gene fusions are defined as those predicted to translate into a
fusion protein with a functional TRKA/B/C or ROS1 kinase domain, without a
concomitant second oncodriver as determined by a nucleic acid-based
diagnostic testing method

3. Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse

4. Archival tumor tissue from diagnosis or, preferably, at relapse

5. Performance status: Lansky or Karnofsky score ≥ 60% and minimum life expectancy of at
least 4 weeks

6. Prior therapy: Participants must have a disease that is locally advanced, metastatic,
or where surgical resection is likely to result in severe morbidity, and who have no
satisfactory treatment options for solid tumors and primary CNS tumors that are
neurotrophic tyrosine receptor kinase (NTRK) or ROS1 fusion-positive

7. Participants must have recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to enrollment

8. Adequate organ and neurologic function

9. Females of childbearing potential must have a negative serum pregnancy test during
screening and be neither breastfeeding nor intending to become pregnant during study
participation. Agreement to remain abstinent or use use combined contraceptive methods
prior to study entry, for the duration of study participation and in the following 90
days after discontinuation of study treatment.

10. For male participants with a female partner of childbearing potential or a pregnant
female partner: Agreement to remain abstinent or use a condom during the treatment
period and for at least 3 months after the last dose of study drug

Exclusion Criteria:

1. Receiving other experimental therapy

2. Known congenital long QT syndrome

3. History of recent (3 months) symptomatic congestive heart failure or ejection fraction
≤50% at screening

4. Known active infections

5. Familial or personal history of congenital bone disorders, bone metabolism alterations
or osteopenia

6. Receiving Enzyme Inducing Antiepileptic Drugs (EIAEDs) within 14 days of first dose.

7. Prior treatment with approved or investigational TRK or ROS1 inhibitors

8. Known hypersensitivity to entrectinib or any of the other excipients of the
investigational medicinal product

9. Patients with NB with bone marrow space-only disease

10. Incomplete recovery from acute effects of any surgery prior to treatment.

11. Active gastrointestinal disease or other malabsorption syndromes that would impact
drug absorption.

12. Other severe acute or chronic medical or psychiatric condition or lab abnormality that
may increase the risk associated with study participation, drug administration or may
interfere with the interpretation of study results.

16-045