marked.bio

TRK inhibitor · small molecule

larotrectinib

8 active trials across 7 of our biomarkers, targeting TRK. 2 active approvals for a biomarker on marked.bio.

Also known as LOXO-101, BAY 2757556, Vitrakvi.

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
larotrectinib
FDA, 2018
NTRK gene fusion, no acquired resistance mutation, no satisfactory alternatives AA 26/11/2018, converted to regular approval 09/04/2025 (FDA Verified clinical benefit list). The DailyMed label reached (revised 12/2018) is outdated and still shows the accelerated-approval statement. Source
EU (EMA), 2019
NTRK gene fusion, no satisfactory alternatives Conditional MA 19/09/2019. Source
Vitrakvi 		NTRK1/2/3 fusion solid tumours (tumour-agnostic) Approved 2018 Approved 2019 conditional

In the US label

LOXO-TRK-14001, SCOUT and NAVIGATE (pooled) single-arm, 339 patients
Response 60% (55-65)Lasting 43.3 months

Stopped for side effects 12%

Trial details and side effects
Patients
NTRK fusion-positive solid tumours, adults and children (NCT02576431)
Most common side effects
AST increase 62%, ALT increase 61%, anaemia 45%, musculoskeletal pain 41%, fatigue 31%, vomiting 30% (444 patients)
Notes
Complete responses 24%. Grade 3-4 side effects in 60%. US label rev. 04/2025.
Source
US label

In the EU product information

LOXO-TRK-14001, SCOUT and NAVIGATE (pooled) single-arm, 304 (364 incl. brain tumours)
Response 65% (60% incl. brain tumours) (59-70)Lasting 43.3 months

Trial details and side effects
Patients
NTRK fusion-positive solid tumours, adults and children (NCT02576431)
Most common side effects
AST increase 62%, ALT increase 61%, anaemia 45%, musculoskeletal pain 41%, fatigue 31%, vomiting 30% (444 patients)
Notes
EU SmPC section 5.1 (pooled, conditional authorisation). Complete responses 22%. Side effects from the US label.
Source
EU product information

Biomarkers

BiomarkerActive trialsAll trialsFurthest active phase
NTRK1/2/3 fusion 8 10 Phase 4
BRAF V600E 2 2 Phase 4
RET fusion or mutation 2 2 Phase 4
ALK fusion 1 1 Phase 2
EGFR exon 20 insertion 1 1 Phase 2
KRAS G12C 1 1 Phase 2
ROS1 fusion 1 1 Phase 2

Sponsors

Industry sponsors leading active biomarker-selected trials of larotrectinib.

  1. Bayer 1

Trials

8 of 10 trials shown

  1. Genotype-Driven Neoadjuvant Therapy for Locally Advanced Thyroid Cancer: A Real-World Cohort Study

    Not yet recruiting Phase 4 Fujian Medical University Started 2025Primary completion 2027-12 NCT07010393

    dabrafenib FDA EUtrametinib FDA EUselpercatinibpralsetiniblenvatiniblarotrectinibanlotinibpembrolizumabsintilimabcabozantinibBemosuzumab

    BRAF V600E mutation

    BRAF V600ERET fusion or mutationNTRK1/2/3 fusionThyroid Neoplasms

  2. Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations.

    Recruiting Phase 2 Sun Yat-sen University Started 2024Primary completion 2027-11 NCT06563999

    sunvozertinib FDAcrizotinibpralsetiniblarotrectinibsavolitinibpyrotinibdabrafenibtrametinibglecirasibensartinib

    Subjects should have a rare mutation based on NGS, including mutations of EGFR exon20ins, ROS1 fusion, RET fusion, NTRK fusion, MET 14 exon, HER2, BRAF V600E, KRAS G12C, and ALK …

    EGFR exon 20 insertionKRAS G12CBRAF V600EALK fusionROS1 fusionRET fusion or mutationNTRK1/2/3 fusionLung Cancer Stage III, Mutation

  3. Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer

    Recruiting Phase 2 Children's Hospital of Philadelphia Started 2024Primary completion 2028-10 NCT05783323

    larotrectinib FDA EU

    Identification of an neurotrophic tyrosine receptor kinase (NTRK) (NTRK1, NTRK2, or NTRK3) gene fusion in a CLIA/CAP accredited laboratory without known kinase domain resistance mutation

    NTRK1/2/3 fusionDifferentiated Thyroid Cancer, Pediatric Cancer, Cancer, Cancer, Thyroid

  4. Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia

    Active, not recruiting Phase 2 Children's Oncology Group Started 2019Primary completion 2024-09 NCT03834961

    larotrectinib FDA EU

    …ients must have a histologic diagnosis of infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified in a Clinical Laboratory Improvement Act/College of American Pathologists (CLI…

    NTRK1/2/3 fusionCentral Nervous System Neoplasm, Infantile Fibrosarcoma, Recurrent Acute Leukemia, Refractory Acute Leukemia

  5. Testing LOXO-101 as Potentially Targeted Treatment in Cancers With NTRK Genetic Changes (MATCH - Subprotocol Z1E)

    Active, not recruiting Phase 2 National Cancer Institute (NCI) Started 2017Primary completion 2023-04 NCT06390852

    larotrectinib FDA EU

    Patients must have a malignancy harboring an NTRK1, NTRK2 or NTRK3 gene fusion, as determined by the MATCH screening assessment

    NTRK1/2/3 fusionAdvanced Lymphoma, Advanced Malignant Solid Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm

  6. Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)

    Active, not recruiting Phase 2 National Cancer Institute (NCI) Started 2017Primary completion 2024-09 NCT03213704

    larotrectinib FDA EU

    … or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)

    NTRK1/2/3 fusionAdvanced Malignant Solid Neoplasm, Recurrent Ependymoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Glioma

  7. A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children

    Active, not recruiting Phase 1/2 Bayer Started 2015Primary completion 2024-07 NCT02637687

    larotrectinib FDA EU

    OR Infants from birth and older with a diagnosis of malignancy and with a documented NTRK fusion that has progressed or was nonresponsive to available therapies, and for which no standar…

    NTRK1/2/3 fusionSolid Tumors Harboring NTRK Fusion

  8. A Pilot Study of Larotrectinib for Newly-Diagnosed High-Grade Glioma With NTRK Fusion

    Recruiting Early Phase 1 Nationwide Children's Hospital Started 2021Primary completion 2026-12 NCT04655404

    larotrectinib FDA EU

    …eptomeningeal disease only, with no definitive identifiable primary tumor, and documented NTRK fusion, must be discussed with the Study Chair on a case-by-case basis.

    NTRK1/2/3 fusionHigh Grade Glioma, Diffuse Intrinsic Pontine Glioma