This Roche’s sponsored study was a 5-part, open-label, Phase 1/2 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.

The Study Details

  • Phase I
  • 65 Participants
  • Start Date: May 3, 2016
  • Estimated Primary Completion Date June 2023
  • Research Sites:  23

Study Summary

In this phase 1/1b trial, entrectinib showed antitumor activity and appeared to be safe in pediatric patients with recurrent or refractory solid tumors harboring NTRK1/2/3, ROS1, or ALK aberrations, including those in the central nervous system.  The trial results will be presented at the upcoming 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Cancer Therapy Advisor reports a total of 29 children and adolescents with solid tumors were enrolled in the trial and received entrectinib, an oral inhibitor of TRKA/B/C, ROS1, and ALK proteins that can penetrate CNS.  This trial consisted of two phases including:

  • A dose-finding phase that established a recommended dose of 550 mg/m2 daily, and a basket trial that is currently ongoing.
  • 28 patients were evaluable for a response:
  • All patients (11 of 11) harboring a NTRK1/2/3, ROSI or ALK gee fusion had responses (3 complete responses and 8 partial responses)
  • One patient with an ALK-mutated neuroblastoma responded to treatment with entrectinib
  • No responses were seen in patients with tumors lacking aberrations target kinases


Giles W. Robinson, MD, a pediatric neuro-oncologist at St. Jude’s Children’s Research Hospital in Memphis, TN said “This is early results and many of our patients continue to derive a benefit from this study.”

Entrectinib Background (acquired by Roche)

Entrectinib (previously known as RXDX-101 and NMS-E628) is an investigational drug with preliminary antitumor activity. It is a selective tyrosine kinase inhibitor (TKI), of the tropomyosin receptor kinases (Trk) A, B and C, C-ros oncogene 1 (ROS1) and anaplastic lymphoma kinase (ALK).

In the U.S., entrectinib has orphan drug designation and rare pediatric disease designation for the treatment of neuroblastoma and orphan drug designation for treatment of TrkA-, TrkB-, TrkC-, ROS1- and ALK-positive non-small cell lung cancer(NSCLC) and metastatic colorectal cancer (mCRC). It has an EU orphan designation for neuroblastoma.

Investigations of entrectinib have been conducted by Ignyta Pharmaceuticals, a San Diego-based drug maker. Ignyta, Inc., (Nasdaq: RXDX) which is an oncology biotechnology company focusing on the discovery, development, and commercialization of new anti-tumor drugs. On 21 December 2017, Roche announced plans to buy Ignyta for $1.7 billion.

Source: Clinical Trials GOV

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