marked.bio

ROS1/TRK TKI (next generation) · small molecule

repotrectinib

5 active trials across 6 of our biomarkers, targeting ROS1/TRK. 4 active approvals for a biomarker on marked.bio.

Also known as TPX-0005, Augtyro.

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
repotrectinib
FDA, 2024
NTRK gene fusion, age >=12 AA 13/06/2024; still on FDA Ongoing accelerated approvals list (label 1.2). Source
EU (EMA), 2025
NTRK gene fusion, age >=12, after an NTRK inhibitor or limited other options Conditional MA 13/01/2025. Source
Augtyro 		NTRK1/2/3 fusion solid tumours (tumour-agnostic) Approved 2024 accelerated Approved 2025 conditional

In the US label

TRIDENT-1 single-arm, 40 TKI-naive; 48 after a TRK inhibitor
Response 58% (TKI-naive); 50% (after a TRK inhibitor) (41-73; 35-65)Lasting not reached (TKI-naive); 9.9 months (after a TRK inhibitor)

Serious side effects 35%Stopped for side effects 7%Fatal 3.5%

Trial details and side effects
Patients
NTRK fusion-positive solid tumours, age 12 and over (NCT03093116)
Most common side effects
dizziness 65%, dysgeusia 54%, peripheral neuropathy 49%, constipation 38%, dyspnoea 30%, fatigue 30% (426 (pooled) patients)
Notes
Accelerated approval. US label rev. 06/2024.
Source
US label

In the EU product information

TRIDENT-1 single-arm, 51 TKI-naive; 69 after a TRK inhibitor
Response 59% (TKI-naive); 48% (after a TRK inhibitor) (44-72; 36-60)Lasting not reached (TKI-naive); 9.8 months (after a TRK inhibitor)

Trial details and side effects
Patients
NTRK fusion-positive solid tumours, age 12 and over (NCT03093116)
Most common side effects
dizziness 65%, dysgeusia 54%, peripheral neuropathy 49%, constipation 38%, dyspnoea 30%, fatigue 30% (426 (pooled) patients)
Notes
EU SmPC section 5.1 (TRIDENT-1, conditional authorisation). Side effects from the US label.
Source
EU product information
repotrectinib
FDA, 2023
locally advanced or metastatic, ROS1-positive FDA approval 15/11/2023. Source
EU (EMA), 2025
ROS1-positive advanced NSCLC Conditional MA 13/01/2025. Source
Augtyro 		ROS1 fusion NSCLC Approved 2023 Approved 2025 conditional

In the US label

TRIDENT-1 single-arm, 71 TKI-naive; 56 after 1 ROS1 TKI
Response 79% (TKI-naive); 38% (after a ROS1 TKI) (68-88; 25-52)Lasting 34.1 months (TKI-naive); 14.8 months (after a ROS1 TKI)

Serious side effects 35%Stopped for side effects 7%Fatal 3.5%

Trial details and side effects
Patients
ROS1-positive NSCLC (NCT03093116)
Most common side effects
dizziness 65%, dysgeusia 54%, peripheral neuropathy 49%, constipation 38%, dyspnoea 30%, fatigue 30% (426 (pooled) patients)
Notes
US label rev. 06/2024.
Source
US label

In the EU product information

TRIDENT-1 single-arm, 121 TKI-naive; 107 after a ROS1 TKI
Response 77% (TKI-naive); 49% (after a ROS1 TKI) (68-84; 39-59)Lasting 33.6 months (TKI-naive); 14.8 months (after a ROS1 TKI)

Trial details and side effects
Patients
ROS1-positive NSCLC (NCT03093116)
Most common side effects
dizziness 65%, dysgeusia 54%, peripheral neuropathy 49%, constipation 38%, dyspnoea 30%, fatigue 30% (426 (pooled) patients)
Notes
EU SmPC section 5.1 (TRIDENT-1, later data cut; conditional authorisation). Side effects from the US label.
Source
EU product information

Biomarkers

BiomarkerActive trialsAll trialsFurthest active phase
ROS1 fusion 5 5 Phase 3
NTRK1/2/3 fusion 2 2 Phase 1/2
ALK fusion 1 1 Phase 1/2
EGFR exon 19 deletion / L858R 0 1 –
KRAS G12C 0 1 –
KRAS G12D 0 1 –

Sponsors

Industry sponsors leading active biomarker-selected trials of repotrectinib.

  1. Bristol Myers Squibb 3

Trials

5 of 7 trials shown

  1. A Study of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3)

    Active, not recruiting Phase 3 Bristol Myers Squibb Started 2023Primary completion 2027-02 NCT06140836

    repotrectinib FDA EUcrizotinib FDA EU

    Participant has a ROS1 gene rearrangement/fusion as detected by a local test.

    ROS1 fusionCarcinoma, Non-Small-Cell Lung

  2. Repotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain Metastasis

    Recruiting Phase 2 MedSIR Started 2025Primary completion 2027-03 NCT06315010

    repotrectinib FDA EU

    Patients with confirmed ROS1 rearrangement.

    ROS1 fusionNSCLC, Brain Metastases, ROS1 Gene Rearrangement

  3. Phase II Efficacy Study of Repotrectinib in Frail and/or Elderly Patients With ROS1-rearranged Advanced NSCLC

    Recruiting Phase 2 Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer Started 2024Primary completion 2031-09 NCT06552234

    repotrectinib FDA EU

    …or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC harboring an ROS1 gene rearrangement as by any nucleic acid-based diagnostic testing method (e.g., next-generation sequencing …

    ROS1 fusionNSCLC Stage IV, NSCLC, Stage III

  4. A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations

    Recruiting Phase 1/2 Bristol Myers Squibb Started 2020Primary completion 2026-09 NCT04094610

    repotrectinib FDA EU

    Cohort 3: subjects with advanced solid tumors with ROS1 gene fusions or other ROS1 aberrations (including amplifications and point mutations) with measurable …

    ROS1 fusionNTRK1/2/3 fusionLocally Advanced Solid Tumors, Metastatic Solid Tumors, Lymphoma, Primary CNS Tumors

  5. A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements

    Recruiting Phase 1/2 Bristol Myers Squibb Started 2017Primary completion 2028-02 NCT03093116

    repotrectinib

    …ng primary CNS tumors) (Stage IV, American Joint Committee on Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests.

    ALK fusionROS1 fusionNTRK1/2/3 fusionLocally Advanced Solid Tumors, Metastatic Solid Tumors