ROS1 ROS proto-oncogene 1, receptor tyrosine kinase
ENSG00000047936 · protein coding · Open Targets profile
Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. NELL2 is an endogenous ligand for ROS1. Upon endogenous stimulation by NELL2, ROS1 activates the intracellular signaling pathway and triggers epididymal epithelial differentiation and subsequent sperm maturation (By similarity). May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2. {ECO:0000250|UniProtKB:Q78DX7, ECO:0000269|PubMed:11094073, ECO:0000269|PubMed:16885344}.
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 Withdrawn means the drug was pulled from the market or from development.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, Druggable Family
- Antibody
- UniProt loc high conf, UniProt SigP or TMHMM, GO CC med conf
- PROTAC
- Small Molecule Binder
gnomAD loss of function constraint: o/e 0.9615499973297119 (upper bound 1.0649000406265259). 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 105 registry trials, updated in the last three years, of the most advanced drugs against ROS1 (entrectinib, repotrectinib, crizotinib, taletrectinib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Bristol-Myers SquibbBristol-Myers Squibb · 3 of 4 trials Phase 2+
- Yongchang ZhangHunan Cancer Hospital · 3 of 3 trials Phase 2+
- Caicun ZhouShanghai East Hospital · 2 of 2 trials Phase 2+
- David S HongECOG-ACRIN Cancer Research Group · 2 of 2 trials Phase 2+
- Matthew KrebsThe Christie Hospital · 2 of 2 trials Phase 2+
- Aaron S MansfieldECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
- Aditi BagchiSt. Jude Children's Research Hospital · 1 of 1 trials Phase 2+
- Alice T ShawECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
- Arkadiusz DudekHealth Partners Institute · 1 of 1 trials Phase 2+
- Åslaug HellandOslo University Hospital · 1 of 1 trials Phase 2+
- Daniel J RenoufBCCA - Vancouver Cancer Centre, Vancouver BC, Canada · 1 of 1 trials Phase 2+
- Daniel MoreiraSt. Jude Children's Research Hospital · 1 of 1 trials Phase 2+
- David GerberECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
- Dongmei JiFudan University · 1 of 1 trials Phase 2+
- E.E. VoestThe Netherlands Cancer Institute · 1 of 1 trials Phase 2+
Registry trials of entrectinib, repotrectinib, crizotinib, taletrectinib 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; 59 of 99 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. 6 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
28 trials of drugs against ROS1 were stopped early; 5 give no reason
Terminated, withdrawn and suspended interventional trials of entrectinib, repotrectinib, crizotinib, taletrectinib, 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 28.
- suspended · 2026-06-05 · Megan Kruse, MD · Taletrectinib“Anheart acquired by Nuvation Bio; leadership not moving forward”
- terminated · 2026-04-23 · National Cancer Institute (NCI) · Crizotinib“Inadequate accrual rate”
- terminated · 2026-01-05 · M.D. Anderson Cancer Center · Repotrectinib“<75% Participation”
- terminated · 2025-07-16 · National Cheng-Kung University Hospital · Crizotinib 250 MG“Patients were recruited during screen phase but fewer patients met criteria.”
- withdrawn · 2025-04-01 · Turning Point Therapeutics, Inc. · matched by the registry's drug synonyms“Insufficient enrollment”
- terminated · 2025-01-23 · Pfizer · Crizotinib“Termination of further treatment on the study due to the availability of commercial supply or a rollover study (NCT05160922) that will allow active subjects to continue receiving treatment.”
- terminated · 2024-11-08 · Pfizer · Crizotinib“The trial is terminated based on business decision, not due to safety concerns or regulatory requirements.”
- terminated · 2024-04-26 · Suzhou Zelgen Biopharmaceuticals Co.,Ltd · matched by the registry's drug synonyms“Sponsor R\&D Strategy Adjustment”
- 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“Low accrual”
- withdrawn · 2024-01-23 · OHSU Knight Cancer Institute · Entrectinib“Withdrawn due to a change in therapeutic interventions.”
- terminated · 2023-11-22 · Arkadiusz Z. Dudek, MD · Entrectinib“This study required dose reductions to the lower dose level (Dose level -1). But this dose level (Dose level -1) was not further explored because of lack of funding.”
- withdrawn · 2023-09-26 · Turning Point Therapeutics, Inc. · repotrectinib (TPX-0005)“Insufficient enrollment”
- terminated · 2023-08-07 · Hoffmann-La Roche · matched by the registry's drug synonyms“The data from this study is no longer needed.”
- terminated · 2023-07-07 · Pfizer · Crizotinib“The study was terminated since there was no need for further safety or efficacy data to be collected. The participants having benefit from the Investigational treatments have been moved to a continuation study (NCT05059522)”
- terminated · 2022-11-03 · Wake Forest University Health Sciences · Crizotinib“Study closed to accrual due to low accrual numbers.”
- terminated · 2022-10-24 · University of Colorado, Denver · matched by the registry's drug synonyms“Low accrual”
- terminated · 2021-09-13 · M.D. Anderson Cancer Center · Crizotinib (Xalkori)“PI request”
- terminated · 2020-02-20 · SWOG Cancer Research Network · crizotinib“science has moved forward and there is no intent to complete the study”
- terminated · 2020-01-27 · University of California, San Francisco · Entrectinib“Funding”
- terminated · 2019-12-17 · National Cancer Institute (NCI) · matched by the registry's drug synonymsNo reason given
- terminated · 2019-08-05 · National Cancer Institute (NCI) · CrizotinibNo reason given
- terminated · 2019-07-01 · Pfizer · Crizotinib“Decision based on the low enrollment mainly due to high efficacy drugs available in 1st line ALK-positive NSCLC (eg alectinib), not due to any safety concerns”
- terminated · 2017-08-09 · Mothaffar Rimawi · Crizotinib & Sunitinib 37.5 mg Cohort 3“Poor accrual so the study was halted on May 16, 2017.”
- withdrawn · 2016-12-30 · Jun Zhu · crizotinibNo reason given
Paediatric incentives and obligations for ROS1's drugs
For entrectinib, repotrectinib, crizotinib, taletrectinib: 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: yes · ROS1 is on the list. Membership alone neither requires nor waives a pediatric study.Rule: 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 · 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-001493-PIP03-18-M01 (crizotinib, Treatment of anaplastic large cell lymphoma;Treatment of inflammatory myofibroblastic tumours): PM: decision on the application for modification of an agreed PIP, 27 Jan 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; EMEA-001493-PIP02-18 (crizotinib, Treatment of lung malignant neoplasms): W: decision granting a waiver in all age groups for all conditions or indications, 7 Dec 2018Rule: 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/3/15/1580 withdrawn 11 Nov 2015: Treatment of neuroblastomaRule: 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 EU/3/15/1580, 2026-11-11
- Authorised in the EU: yes · Rozlytrek: authorised since 31 Jul 2020, conditional; Xalkori: authorised since 23 Oct 2012; Augtyro: authorised since 13 Jan 2025, conditionalRule: 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; 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 therapy; Crizotinib [Xalkori], 14 Jul 2022: Treatment of adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive; +1 moreRule: 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 · 30 interventional studies of entrectinib, repotrectinib, crizotinib, taletrectinib include patients under 18; 14 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 4 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.