Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options (STARTRK-NG)

• ClinicalTrials.gov Identifier: NCT02650401
• Recruitment Status: Active, not recruiting
• First Posted: January 8, 2016
• Last Update Posted: March 29, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: January 4, 2016
• First Posted Date: January 8, 2016
• Last Update Posted Date: March 29, 2024
• Actual Study Start Date: May 3, 2016
• Estimated Primary Completion Date: June 15, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 1, 2022)

• Maximum Tolerated Dose (MTD) [ Time Frame: Approximately 6 months ]
  Assessed by National Cancer Institute Common Terminology for Adverse Events Criteria (NCI CTCAE v4.03)
• Recommended Phase 2 Dose (RP2D) of F1 Formulation In Pediatric Participants Able To Swallow Intact Capsules [ Time Frame: Approximately 6 months ]
  Assessed by NCI CTCAE v4.03
• Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric Participants Able To Swallow Intact Capsules [ Time Frame: Approximately 6 months ]
  Assessed by NCI CTCAE v4.03
• Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric In Participants Dosed Via Feeding Tube (Nasogastric Tube Or Gastric Tube) [ Time Frame: Approximately 6 months ]
  Assessed by NCI CTCAE v4.03
• Recommended Phase 2 Dose (RP2D) Of Minitablets/F15 Formulation In Pediatric Participants Unable To Swallow Intact Capsules [ Time Frame: Approximately 6 months ]
  Assessed by NCI CTCAE v4.03
• Cohort B: Objective Response Rate (ORR) [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR
• Cohort D: ORR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR

Original Primary Outcome Measures (submitted: January 7, 2016)

• Maximum Tolerated Dose (MTD) [ Time Frame: Approximately 6 months ]
  Assessed by National Cancer Institute Common Terminology for Adverse Events Criteria (NCI CTCAE v4.03)
• Recommended Phase 2 Dose (RP2D) [ Time Frame: Approximately 6 months ]
  Assessed by NCI CTCAE v4.03

Current Secondary Outcome Measures (submitted: May 1, 2022)

• Safety and Tolerability - AE, ECG and Labs assessed by NCI CTCAE v4.03 [ Time Frame: Approximately 24 months ]
  AE, ECG and Labs assessed by NCI CTCAE v4.03
• Maximum observed plasma drug concentration (Cmax) using F1 Formulation [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Maximum observed plasma drug concentration (Cmax) using F06 Formulation given intact [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Maximum observed plasma drug concentration (Cmax) using F06 Formulation administered via feeding tube [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Maximum observed plasma drug concentration (Cmax) using minitablets/F15 [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Time to Cmax, by inspection (Tmax) using F1 Formulation [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Time to Cmax, by inspection (Tmax) using F06 Formulation given intact [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Time to Cmax, by inspection (Tmax) using F06 Formulation administered via feeding tube [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Time to Cmax, by inspection (Tmax) using minitablets/F15 [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• AUC at steady state (AUCss) using F1 Formulation [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• AUC at steady state (AUCss) using F06 Formulation given intact [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• AUC at steady state (AUCss) using F06 Formulation administered via feeding tube [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• AUC at steady state (AUCss) using minitablets/F15 [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Terminal half life (t½) using F1 Formulation [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Terminal half life (t½) using F06 Formulation given intact [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Terminal half life (t½) using F06 Formulation administered via feeding tube [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Terminal half life (t½) using minitablets/F15 [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Area under the drug concentration by time curve (AUC) using F1 Formulation [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Area under the drug concentration by time curve (AUC) using F06 Formulation given intact [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Area under the drug concentration by time curve (AUC) using F06 Formulation administered via feeding tube [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Area under the drug concentration by time curve (AUC) using minitablets/F15 [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter
• Cohort A, D, or E: Clinical Benefit Rate (CBR) [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Cohort B or E: CBR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Cohort C: CBR [ Time Frame: Approximately 6 months ]
  Assessed by the Curie scale per the BICR and investigator
• Cohort A, D, or E: Progression-free Survival (PFS) [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Cohort B or E: PFS [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Cohort C: PFS [ Time Frame: Approximately 6 months ]
  Assessed by the Curie scale per the BICR and investigator
• Cohort A, D, or E: Overall Survival (OS) [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1
• Cohort B or E: OS [ Time Frame: Approximately 6 months ]
  Assessed by RANO
• Cohort A, D, or E: ORR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Cohort B or E: ORR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Cohort C: ORR [ Time Frame: Approximately 6 months ]
  Assessed by the Curie scale per the BICR and investigator
• Cohort A, D, or E: Time to response (TTR) [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Cohort B or E: TTR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Cohort C: TTR [ Time Frame: Approximately 6 months ]
  Assessed by the Curie scale per the BICR and investigator
• Cohort A, D, or E: Duration of Response (DOR) [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Cohort B or E: DOR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Cohort C: DOR [ Time Frame: Approximately 6 months ]
  Assessed by the Curie scale per the BICR and investigator
• Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): ORR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the investigator
• Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort D or E): ORR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the investigator
• Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort A, D, or E): ORR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort B or E): ORR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Phase 1/2 Participants with ROS1 gene fusions (Cohort A, D, or E): ORR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Phase 1/2 Participants with ROS1 gene fusions (Cohort B or E): ORR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort A, D, or E): ORR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): ORR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): DOR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort D or E): DOR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort A, D, or E): DOR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort B or E): DOR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Phase 1/2 Participants with ROS1 gene fusions (Cohort A, D, or E): DOR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Phase 1/2 Participants with ROS1 gene fusions (Cohort B or E): DOR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort A, D, or E): DOR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): DOR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): TTR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort D or E): TTR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort A, D, or E): TTR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort B or E): TTR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Phase 1/2 Participants with ROS1 gene fusions (Cohort A, D, or E): TTR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Phase 1/2 Participants with ROS1 gene fusions (Cohort B or E): TTR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator
• Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort A, D, or E): TTR [ Time Frame: Approximately 6 months ]
  Assessed by RECIST v1.1 per the BICR and investigator
• Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): TTR [ Time Frame: Approximately 6 months ]
  Assessed by RANO per the BICR and investigator

Original Secondary Outcome Measures (submitted: January 7, 2016)

• Safety and Tolerability - AE, ECG and Labs assessed by NCI CTCAE v4.03 [ Time Frame: Approximately 24 months ]
  AE, ECG and Labs assessed by NCI CTCAE v4.03
• Maximum observed plasma drug concentration (Cmax) [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)
• Time to Cmax, by inspection (Tmax) [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)
• Css [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)
• Terminal half life (t½) [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)
• Area under the drug concentration by time curve (AUC) [ Time Frame: Approximately 24 months ]
  Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)
• Objective Response Rate (ORR) [ Time Frame: Approximately 24 months ]
  Assessed by RECIST v1.1
• Progression-free Survival (PFS) [ Time Frame: Approximately 24 months ]
  Defined as time from the date of study enrollment to the first occurrence of objective disease progression or date of death due to any cause, whichever occurs first

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options
• Official Title: A Phase 1/2, Open-Label, Dose-Escalation And Expansion Study Of Entrectinib (Rxdx-101) In Pediatrics With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Solid Tumors
• CNS Tumors

Intervention

Drug: Entrectinib

TRKA/B/C, ROS1, and ALK inhibitor

Other Name: RXDX-101

Study Arms

• Active Comparator: Extracranial solid tumors harboring NTRK1/2/3,

  Arm closed for further enrollment

  ROS1, ALK non-gene fusion molecular alterations

  Oral entrectinib (RXDX-101)

  Intervention: Drug: Entrectinib
• Active Comparator: CNS tumors harboring- NTRK1/2/3, ROS1, ALK

  Arm closed for further enrollment

  molecular alterations, including gene fusions

  Oral entrectinib (RXDX-101)

  Intervention: Drug: Entrectinib
• Active Comparator: Neuroblastoma

  Arm closed for further enrollment

  Oral entrectinib (RXDX-101)

  Intervention: Drug: Entrectinib
• Active Comparator: Non-neuroblastoma, extracranial solid tumors

  Arm closed for further enrollment

  harboring - NTRK1/2/3, ROS1, ALK gene fusions

  Oral entrectinib (RXDX-101)

  Intervention: Drug: Entrectinib
• Active Comparator: Any participant unable to swallow capsules

  Arm closed for further enrollment

  Any participant who otherwise meet all other eligibility criteria

  Oral entrectinib (RXDX-101)

  Intervention: Drug: Entrectinib
• Active Comparator: Expansion: CNS tumors harboring NTRK1/2/3, ROS1

  gene fusions

  Oral entrectinib (RXDX-101)

  Intervention: Drug: Entrectinib
• Active Comparator: Expansion: Extracranial solid tumors harboring NTRK1/2/3, ROS1

  NTRK 1,2,3 and ROS1 fusions

  Oral entrectinib (RXDX-101)

  Intervention: Drug: Entrectinib

Publications *

• Desai AV, Robinson GW, Gauvain K, Basu EM, Macy ME, Maese L, Whipple NS, Sabnis AJ, Foster JH, Shusterman S, Yoon J, Weiss BD, Abdelbaki MS, Armstrong AE, Cash T, Pratilas CA, Corradini N, Marshall LV, Farid-Kapadia M, Chohan S, Devlin C, Meneses-Lorente G, Cardenas A, Hutchinson KE, Bergthold G, Caron H, Chow Maneval E, Gajjar A, Fox E. Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG). Neuro Oncol. 2022 Oct 3;24(10):1776-1789. doi: 10.1093/neuonc/noac087.
• Doebele RC, Drilon A, Paz-Ares L, Siena S, Shaw AT, Farago AF, Blakely CM, Seto T, Cho BC, Tosi D, Besse B, Chawla SP, Bazhenova L, Krauss JC, Chae YK, Barve M, Garrido-Laguna I, Liu SV, Conkling P, John T, Fakih M, Sigal D, Loong HH, Buchschacher GL Jr, Garrido P, Nieva J, Steuer C, Overbeck TR, Bowles DW, Fox E, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Demetri GD; trial investigators. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020 Feb;21(2):271-282. doi: 10.1016/S1470-2045(19)30691-6. Epub 2019 Dec 11. Erratum In: Lancet Oncol. 2020 Feb;21(2):e70. Lancet Oncol. 2020 Jul;21(7):e341. Lancet Oncol. 2020 Aug;21(8):e372. Lancet Oncol. 2021 Oct;22(10):e428.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 13, 2023): 69
• Original Estimated Enrollment (submitted: January 7, 2016): 80
• Estimated Study Completion Date: June 15, 2025
• Estimated Primary Completion Date: June 15, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 0 Years to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, China, France, Germany, Hong Kong, Italy, Korea, Republic of, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT02650401
• Other Study ID Numbers: RXDX-101-03; CO40778 ( Other Identifier: Hoffmann-La Roche )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: March 2024