NTRK1 neurotrophic receptor tyrosine kinase 1
ENSG00000198400 · protein coding · Open Targets profile
Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand (PubMed:1281417, PubMed:15488758, PubMed:17196528, PubMed:1849459, PubMed:1850821, PubMed:22649032, PubMed:27445338, PubMed:8325889). Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity). Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:1281417). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors. {ECO:0000250|UniProtKB:P35739, ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:1849459, ECO:0000269|PubMed:1850821, ECO:0000269|PubMed:22649032, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:8155326, ECO:0000269|PubMed:8325889}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- Literature, UniProt Ubiquitination, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.7142999768257141 (upper bound 0.8824899792671204). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 257 registry trials, updated in the last three years, of the most advanced drugs against NTRK1 (entrectinib, larotrectinib, lestaurtinib, repotrectinib, cenegermin, regorafenib, taletrectinib, pegcantratinib, milciclib, GZ-389988), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Flavio MantelliDompé Farmaceutici S.p.A · 6 of 7 trials Phase 2+Ph2NCT06244316 · A Safety and Efficacy Study of 2 Dosing Regimens of Recombinant Human Nerve Growth Factor (rhNGF) Eye Drop Solution Compared With Vehicle in Patients With Dry Eye Disease.brief
- Bristol-Myers SquibbBristol-Myers Squibb · 3 of 4 trials Phase 2+
- Kanwal RaghavM.D. Anderson Cancer Center · 3 of 3 trials Phase 2+Ph2NCT07071961 · Regorafenib (Reg) and Lorigerlimab (Lor), RELO Regimen, in Treatment of High-risk Patients With Colorectal Cancer With Radiographic Occult Molecular Residual Disease After End of Established Definitive Therapy [ReLOAD Trial]brief
- Marwan G FakihCity of Hope Medical Center · 2 of 3 trials Phase 2+Ph1/Ph2NCT05672316 · Botensilimab, Balstilimab and Regorafenib for the Treatment of Patients With Microsatellite Stable Metastatic Colorectal Cancer Who Have Progressed on Prior Chemotherapybrief
- David S HongECOG-ACRIN Cancer Research Group · 2 of 2 trials Phase 2+
- Lin ShenPeking University Cancer Hospital & Institute · 2 of 2 trials Phase 2+
- Matthew KrebsThe Christie Hospital · 2 of 2 trials Phase 2+
- Nicolas PENELCentre Oscar Lambret · 2 of 2 trials Phase 2+
- Ying YuanSecond Affiliated Hospital, Zhejiang University, School of Medicine · 2 of 2 trials Phase 2+
- Florence DUFFAUDLa Timone University Hospital · 1 of 2 trials Phase 2+
- Jean-Yves BLAYCentre Leon Berard · 1 of 2 trials Phase 2+
- Abdullah EsmailHouston Methodist Neal Cancer Center · 1 of 1 trials Phase 2+
- Aditi BagchiSt. Jude Children's Research Hospital · 1 of 1 trials Phase 2+
- Aiping ZhouCancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College · 1 of 1 trials Phase 2+
- Alan HoMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
Registry trials of entrectinib, larotrectinib, lestaurtinib, repotrectinib, cenegermin, regorafenib, taletrectinib, pegcantratinib, milciclib, GZ-389988 updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 177 of 236 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 21 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
61 trials of drugs against NTRK1 were stopped early; 11 give no reason
Terminated, withdrawn and suspended interventional trials of entrectinib, larotrectinib, lestaurtinib, repotrectinib, cenegermin, regorafenib, taletrectinib, pegcantratinib, milciclib, GZ-389988, selitrectinib, altiratinib, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 61.
- terminated · 2026-11-03 · Peking University Cancer Hospital & Institute · regorafenib“The study was stopped early due to lack of efficacy.”
- suspended · 2026-10-20 · City of Hope Medical Center · Regorafenib“resources”
- terminated · 2026-10-05 · Children's Oncology Group · Regorafenib“Drug supply issues”
- terminated · 2026-08-26 · Bristol-Myers Squibb · RegorafenibNo reason given
- terminated · 2026-07-06 · Syndax Pharmaceuticals · matched by the registry's drug synonyms“Study was terminated by sponsor after Phase 1b as pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort.”
- withdrawn · 2026-06-15 · University of Miami · Regorafenib“Investigator decision”
- suspended · 2026-06-05 · Megan Kruse, MD · Taletrectinib“Anheart acquired by Nuvation Bio; leadership not moving forward”
- withdrawn · 2026-03-11 · M.D. Anderson Cancer Center · Regorafenib“0 participants enrolled”
- terminated · 2026-03-09 · Translational Research in Oncology · Regorafenib in combination with pembrolizumab“The trial ended earlier than planned due to slow enrolment, which has made it unfeasible to achieve the target sample size within a reasonable timeframe. Consequently, a business decision has been made to discontinue funding for the trial.”
- terminated · 2026-03-05 · Wake Forest University Health Sciences · Regorafenib“Slow accruals”
- withdrawn · 2026-02-25 · M.D. Anderson Cancer Center · Regorafenib“0 participants enrolled”
- terminated · 2026-01-20 · Anwaar Saeed · Regorafenib“Terminated per directive from Bayer due to funding.”
- terminated · 2026-01-05 · M.D. Anderson Cancer Center · Repotrectinib“<75% Participation”
- withdrawn · 2025-04-01 · Turning Point Therapeutics, Inc. · matched by the registry's drug synonyms“Insufficient enrollment”
- terminated · 2025-03-30 · UNICANCER · Regorafenib then Trifluridine/Tipiracil, Trifluridine/Tipiracil then Regorafenib“Following the presentation of the SUNLIGHT study results at ASCO GI and the rapid change in patient management in the majority of centers, the IDMC experts recommended halting inclusion in the SOREGATT study with immediate effect.”
- terminated · 2025-03-11 · Great Novel Therapeutics Biotech & Medicals Corporation · Regorafenib“The overall profile does not support development for Hepatocellular Carcinoma”
- terminated · 2024-12-11 · ImmunityBio, Inc. · Regorafenib“low enrollment”
- withdrawn · 2024-12-02 · Dompé Farmaceutici S.p.A · matched by the registry's drug synonyms“The study was withdrawn prior to enrolling subjects due to realignment of strategic priorities.”
- withdrawn · 2024-11-21 · City of Hope Medical Center · Regorafenib“Abandoned 9/23/24”
- terminated · 2024-06-26 · Wake Forest University Health Sciences · Regorafenib“Funder terminated.”
- terminated · 2024-06-05 · Theseus Pharmaceuticals · matched by the registry's drug synonyms“The Sponsor terminated the study due to early dose-limiting toxicities.”
- withdrawn · 2024-04-29 · M.D. Anderson Cancer Center · Regorafenib“0 participant accrual”
- terminated · 2024-04-02 · Turning Point Therapeutics, Inc. · matched by the registry's drug synonyms“Inability to achieve and optimize a dose that could provide a positive benefit risk profile”
- terminated · 2024-03-04 · OHSU Knight Cancer Institute · Entrectinib, Regorafenib“Low accrual”
- terminated · 2024-02-07 · Dana-Farber Cancer Institute · matched by the registry's drug synonyms“Difficulty with patient recruitment”
Paediatric incentives and obligations for NTRK1's drugs
For entrectinib, larotrectinib, lestaurtinib, repotrectinib, cenegermin, regorafenib, taletrectinib, pegcantratinib, milciclib, GZ-389988, selitrectinib, altiratinib: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · NTRK1 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000182170 (regorafenib, Treatment of all conditions contained in the category of malignant neoplasms (except haematopoietic and lymphoid tissue)): PM: decision on the application for modification of an agreed PIP, 5 Dec 2024; EMEA-002096-PIP01-16-M03 (Entrectinib, Treatment of all conditions included in the category of malignant neoplasms (except haematopoietic and lymphoid tissue neoplasms)): PM: decision on the application for modification of an agreed PIP, 8 Sept 2021; compliance positive 24 Feb 2023; EMEA-001971-PIP02-16-M04 (Larotrectinib, Treatment of all conditions included in the category of malignant neoplasms (except central nervous system tumours, haematopoietic and lymphoid tissue neoplasms)): PM: decision on the application for modification of an agreed PIP, 3 Dec 2021; compliance positive 31 Mar 2023; EMEA-002635-PIP02-21-M02 (repotrectinib, Treatment of all conditions included in the category of malignant neoplasms (except haematopoietic neoplasms)): PM: decision on the application for modification of an agreed PIP, 9 Aug 2023; +2 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/19/2177 withdrawn 28 Jun 2019: Treatment of glioma; EU/3/12/1059 withdrawn 8 Nov 2012: Treatment of malignant thymoma; EU/3/18/1995 withdrawn 21 Mar 2018: Treatment of salivary gland cancer; EU/3/15/1606 withdrawn 11 Jan 2016: Treatment of soft tissue sarcoma; +5 moreRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Rozlytrek: authorised since 31 Jul 2020, conditional; Vitrakvi: authorised since 19 Sept 2019, conditional; Stivarga: authorised since 26 Aug 2013; Augtyro: authorised since 13 Jan 2025, conditional; +1 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: yes · Entrectinib [Rozlytrek], 20 Oct 2023: Treatment of adult and pediatric patients older than 1 month with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory standard therapy; Larotrectinib [Vitrakvi], 26 Nov 2018: Treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment; Repotrectinib [Augtyro], 13 Jun 2024: Treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapyRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 38 interventional studies of entrectinib, larotrectinib, lestaurtinib, repotrectinib, cenegermin, regorafenib, taletrectinib, pegcantratinib, milciclib, gz-389988, selitrectinib, altiratinib include patients under 18; 25 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 17 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.