Study of RXDX-101 in Children With Recurrent or Refractory Solid Tumors and Primary CNS Tumors, With or Without TRK, ROS1, or ALK Fusions

This is a 5-part, open-label, Phase 1 / 1b multicenter, dose escalation study in pediatric patients with relapsed refractory solid tumors; 2) primary CNS tumors; 3) neuroblastoma; 4) non-neuroblastoma, extracranial solid tumors with NTRK1 / 2 / 3, ROS1 or ALK gene rearrangements; and 5) patients who are otherwise eligible but unable to swallow capsules. The study is designed to explore the safety, maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D), pharmacokinetics, and antitumor activity of entrectinib.

Inclusion Criteria

• Inclusion Criteria: 1. Ability to swallow capsules unless enrolled in Part E 2. Body surface area (BSA): Subjects must have a body surface area ≥ 0.45 m2 at the time of the study enrollment, unless enrolled in Part E 3. Disease status: Subjects must have measurable or evaluable disease, by RECIST v1.1 ± Curie Scale Criteria or RANO/RANO-BM 4. Tumor type: - Part A: Relapsed or refractory extracranial solid tumors and (Phase 1b expansion) relapsed or refractory extracranial solid tumors with molecular alterations, non-gene fusions; - Part B: Relapsed or refractory primary CNS tumors with molecular alterations, including gene fusions, documented by a CLIA-approved lab prior to enrollment; - Part C: Relapsed or refractory neuroblastoma; - Part D: Relapsed or refractory non-neuroblastoma, extracranial solid tumors with NTRK1/2/3, ROS1, or ALK gene fusions documented by a CLIA-approved lab prior to enrollment; - Part E: Any patient unable to swallow capsules who otherwise meet all other eligibility criteria for Part A (expansion) B, C or D 5. Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse 6. Archival tumor tissue from diagnosis or, preferably, at relapse 7. Age: Male or female age ≥ 2 years and < 22 years unless enrolled in Part E 8. Performance status: Lansky or Karnofsky score ≥ 60% and minimum life expectancy of at least 4 weeks 9. Patient's cancer must have relapsed after or failed to respond to frontline curative therapy or there must not be other potentially curative treatment options available 10. Adequate organ and neurologic function 11. Females of child bearing potential must have a negative serum pregnancy test within 14 days prior to entrectinib dosing Exclusion Criteria: 1. Receiving other experimental therapy 2. Known congenital long QT syndrome 3. Known active infections 4. Receiving Enzyme Inducing Antiepileptic Drugs (EIAEDs) within 14 days of first dose. 5. Incomplete recovery from acute effects of any surgery prior to treatment. 6. Active gastrointestinal disease or other malabsorption syndromes that would impact drug absorption. 7. 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.

Exclusion Criteria

• Inclusion Criteria: 1. Ability to swallow capsules unless enrolled in Part E 2. Body surface area (BSA): Subjects must have a body surface area ≥ 0.45 m2 at the time of the study enrollment, unless enrolled in Part E 3. Disease status: Subjects must have measurable or evaluable disease, by RECIST v1.1 ± Curie Scale Criteria or RANO/RANO-BM 4. Tumor type: - Part A: Relapsed or refractory extracranial solid tumors and (Phase 1b expansion) relapsed or refractory extracranial solid tumors with molecular alterations, non-gene fusions; - Part B: Relapsed or refractory primary CNS tumors with molecular alterations, including gene fusions, documented by a CLIA-approved lab prior to enrollment; - Part C: Relapsed or refractory neuroblastoma; - Part D: Relapsed or refractory non-neuroblastoma, extracranial solid tumors with NTRK1/2/3, ROS1, or ALK gene fusions documented by a CLIA-approved lab prior to enrollment; - Part E: Any patient unable to swallow capsules who otherwise meet all other eligibility criteria for Part A (expansion) B, C or D 5. Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse 6. Archival tumor tissue from diagnosis or, preferably, at relapse 7. Age: Male or female age ≥ 2 years and < 22 years unless enrolled in Part E 8. Performance status: Lansky or Karnofsky score ≥ 60% and minimum life expectancy of at least 4 weeks 9. Patient's cancer must have relapsed after or failed to respond to frontline curative therapy or there must not be other potentially curative treatment options available 10. Adequate organ and neurologic function 11. Females of child bearing potential must have a negative serum pregnancy test within 14 days prior to entrectinib dosing Exclusion Criteria: 1. Receiving other experimental therapy 2. Known congenital long QT syndrome 3. Known active infections 4. Receiving Enzyme Inducing Antiepileptic Drugs (EIAEDs) within 14 days of first dose. 5. Incomplete recovery from acute effects of any surgery prior to treatment. 6. Active gastrointestinal disease or other malabsorption syndromes that would impact drug absorption. 7. 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.

Lead Organization
Ignyta Inc