marked.bio

TRK/ROS1 TKI · small molecule

entrectinib

8 active trials across 7 of our biomarkers, targeting TRK/ROS1/ALK. 4 active approvals for a biomarker on marked.bio.

Also known as RXDX-101, Rozlytrek.

Counts only trials that select patients by one of the biomarkers on marked.bio, not every trial of this drug.

Approvals and pivotal results

Biomarker-selected approvals in the United States and the European Union, with the pivotal trial's results and side effects where we have them. Results from different trials are not directly comparable.

TherapyBiomarkerTumourUnited StatesEuropean Union
entrectinib
FDA, 2019
NTRK gene fusion, no known acquired resistance mutation, adults and children >1 month AA 15/08/2019 (age >=12), expanded to >1 month by AA 20/10/2023; still accelerated (label 1.2, FDA Ongoing list). Source
EU (EMA), 2020
NTRK gene fusion, no prior NTRK inhibitor, no satisfactory alternatives Conditional MA 31/07/2020. Age extended to >=1 month by X/0017/G (EC 27/06/2024), but the EPAR web page indication text still says >=12 years. Check the SmPC. Source
Rozlytrek 		NTRK1/2/3 fusion solid tumours (tumour-agnostic) Approved 2019 accelerated Approved 2020 conditional

In the US label

ALKA, STARTRK-1 and STARTRK-2 (pooled) single-arm, 54 adults
Response 59% (45-72)Lasting 56% lasting 12 months or more

Serious side effects 39%Stopped for side effects 9%

Trial details and side effects
Patients
NTRK fusion-positive solid tumours (NCT02568267)
Most common side effects
fatigue 48%, constipation 46%, dysgeusia 44%, oedema 40%, dizziness 38%, diarrhoea 35% (355 (pooled) patients)
Notes
Accelerated approval. US label rev. 10/2026.
Source
US label

In the EU product information

ALKA, STARTRK-1 and STARTRK-2 (pooled) single-arm, 242 adults; 44 children
Response 63% (adults); 73% (children) (56-69; 57-85)Lasting 22 months (adults)

Trial details and side effects
Patients
NTRK fusion-positive solid tumours (NCT02568267)
Most common side effects
fatigue 48%, constipation 46%, dysgeusia 44%, oedema 40%, dizziness 38%, diarrhoea 35% (355 (pooled) patients)
Notes
EU SmPC section 5.1 (pooled NTRK, conditional authorisation). Side effects from the US label.
Source
EU product information
entrectinib
FDA, 2019
metastatic, ROS1-positive Label 1.1, regular (no AA statement). Year confirmed: FDA approval announced 15/08/2019. Source
EU (EMA), 2020
ROS1-positive advanced NSCLC, not previously treated with ROS1 inhibitors Conditional MA 31/07/2020 (MA still conditional). Source
Rozlytrek 		ROS1 fusion NSCLC Approved 2019 Approved 2020 conditional

In the US label

ALKA, STARTRK-1 and STARTRK-2 (pooled) single-arm, 92 patients
Response 74% (64-83)Lasting 57% lasting 12 months or more

Serious side effects 39%Stopped for side effects 9%

Trial details and side effects
Patients
ROS1-positive NSCLC (NCT02568267)
Most common side effects
fatigue 48%, constipation 46%, dysgeusia 44%, oedema 40%, dizziness 38%, diarrhoea 35% (355 (pooled) patients)
Notes
US label rev. 10/2026.
Source
US label

In the EU product information

ALKA, STARTRK-1 and STARTRK-2 (pooled) single-arm, 161 patients
Response 67% (59-74)Lasting 16.5 months (patients with 12+ months follow-up)

Trial details and side effects
Patients
ROS1-positive NSCLC (NCT02568267)
Most common side effects
fatigue 48%, constipation 46%, dysgeusia 44%, oedema 40%, dizziness 38%, diarrhoea 35% (355 (pooled) patients)
Notes
EU SmPC section 5.1 (pooled ROS1, later data cut; conditional authorisation). Side effects from the US label.
Source
EU product information

Biomarkers

BiomarkerActive trialsAll trialsFurthest active phase
ROS1 fusion 6 7 Phase 2/3
ALK fusion 3 4 Phase 3
NTRK1/2/3 fusion 3 3 Phase 2
BRAF V600E 2 2 Phase 2
KRAS G12C 2 2 Phase 2
RET fusion or mutation 1 1 Phase 2
BRCA1/2 mutation 0 1 –

Sponsors

Industry sponsors leading active biomarker-selected trials of entrectinib.

  1. Roche 5

Trials

8 of 10 trials shown

  1. DETERMINE Trial Treatment Arm 03: Entrectinib in Adult, Paediatric and Teenage/Young Adult Patients With ROS1 Gene Fusion-Positive Cancers.

    Recruiting Phase 2/3 Cancer Research UK Started 2025Primary completion 2029-10 NCT05770544

    entrectinib FDA EU

    Confirmed diagnosis of a ROS1 gene fusion-positive malignancy, other than NSCLC, that has been identified using an analytically val…

    ROS1 fusionHaematological Malignancy, Malignancy, Malignant Neoplasm, Lymphoproliferative Disorders

  2. A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC)

    Active, not recruiting Phase 3 Roche Started 2022Primary completion 2030-06 NCT05170204

    alectinib FDA EUentrectinibdurvalumab

    …rformed prior and within 42 days for Cohort A2 (ROS1 positive) and 50 days for Cohort A1 (ALK positive) of the first dose of concurrent chemoradiotherapy (cCRT) or sequential chemoradiotherapy…

    ALK fusionROS1 fusionNon-Small Cell Lung Cancer

  3. A Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases

    Active, not recruiting Phase 3 Roche Started 2021Primary completion 2026-09 NCT04603807

    entrectinib FDA EUcrizotinib FDA EU

    … amenable for radical treatment) or metastatic (Stage IV) NSCLC that harbors a documented ROS1 gene rearrangement.

    ROS1 fusionCarcinoma, Non-Small-Cell Lung

  4. Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors

    Recruiting Phase 2 St. Jude Children's Research Hospital Started 2026Primary completion 2027-11 NCT06528691

    entrectinib FDA EUcyclophosphamideetoposidecarboplatinpegfilgrastim

    …h-grade glioma (World Health Organization \[WHO\] grade III or IV) harboring NTRK1/2/3 or ROS1 gene fusions as determined by central pathology review

    ROS1 fusionNTRK1/2/3 fusionHigh Grade Glioma, CNS Tumor

  5. A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC)

    Recruiting Phase 2 Roche Started 2020Primary completion 2026-11 NCT04302025

    alectinibentrectinibvemurafenibcobimetinibpralsetinibatezolizumabSBRTChemotherapydivarasib

    …on in ≥ 1% tumor cells as determined by Food and Drug Administration (FDA)-approved test, KRAS G12C mutation

    KRAS G12CBRAF V600EALK fusionROS1 fusionRET fusion or mutationNTRK1/2/3 fusionNon-small Cell Lung Cancer

  6. Genetic Testing in Guiding Treatment for Patients With Brain Metastases

    Active, not recruiting Phase 2 Alliance for Clinical Trials in Oncology Started 2019Primary completion 2025-11 NCT03994796

    abemaciclibpaxalisibentrectinibadagrasib FDA EU

    Similarly, for patients with KRAS G12C mutations, MRTX849 may be used for newly diagnosed brain metastases.

    KRAS G12CBRAF V600ECDK Gene Mutation, Metastatic Malignant Neoplasm in the Brain, Metastatic Malignant Solid Neoplasm, NTRK Family Gene Mutation

  7. 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

    Active, not recruiting Phase 1/2 Roche Started 2016Primary completion 2027-06 NCT02650401

    entrectinib FDA EU

    Part B: Primary brain tumors with NTRK1/2/3 or ROS1 gene fusions

    ROS1 fusionNTRK1/2/3 fusionSolid Tumors, CNS Tumors

  8. Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)

    Active, not recruiting Phase 2 Roche Started 2015Primary completion 2027-06 NCT02568267

    entrectinib

    …agnosis of locally advanced or metastatic solid tumor that harbors an NTRK1/2/3, ROS1, or ALK gene rearrangement

    ALK fusionBreast Cancer, Cholangiocarcinoma, Colorectal Cancer, Head and Neck Neoplasms