EPHA2 EPH receptor A2
ENSG00000142627 · protein coding · Open Targets profile
Receptor tyrosine kinase which binds promiscuously membrane- bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin- A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand- independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.
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 Withdrawn means the drug was pulled from the market or from development.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, Human Protein Atlas loc
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.5145999789237976 (upper bound 0.6455299854278564). 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 192 registry trials, updated in the last three years, of the most advanced drugs against EPHA2 (vandetanib, regorafenib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- 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
- Lin ShenPeking University Cancer Hospital & Institute · 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+
- 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+
- Alisha H BentM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
- Andrea CercekMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Andrew KennedySCRI Development Innovations, LLC · 1 of 1 trials Phase 2+
- Anna Raciborskathe Institue of Mother and Child · 1 of 1 trials Phase 2+
- Antoine AdenisInstitut régional du cancer de Montpellier · 1 of 1 trials Phase 2+
Registry trials of vandetanib, regorafenib 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; 143 of 176 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. 16 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
73 trials of drugs against EPHA2 were stopped early; 12 give no reason
Terminated, withdrawn and suspended interventional trials of vandetanib, regorafenib, 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 73.
- 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”
- 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 · 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 · 2024-11-21 · 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 · 2024-03-04 · OHSU Knight Cancer Institute · Regorafenib“Low accrual”
- terminated · 2024-02-07 · Dana-Farber Cancer Institute · matched by the registry's drug synonyms“Difficulty with patient recruitment”
- withdrawn · 2024-01-05 · Hoffmann-La Roche · Vandetanib“Due to several logistical challenges during start-up which could not be overcome study was withdrawn.”
- terminated · 2023-11-07 · Hoffmann-La Roche · Regorafenib“The Sponsor made the decision to terminate the study due to start up and recruitment issues caused by limited resource availability at the treating centers.”
- terminated · 2023-10-23 · Case Comprehensive Cancer Center · Regorafenib“PI discretion based on low accrual”
- terminated · 2023-10-16 · UNICANCER · Regorafenib and Irinotecan“Unfavorable benefit-risk balance in the experimental arm following the IDMC for intermediate efficacy and safety analysis”
- withdrawn · 2023-06-07 · Translational Research in Oncology · Regorafenib in combination with Tislelizumab“Study never started/ will not proceed.”
Paediatric incentives and obligations for EPHA2's drugs
For vandetanib, regorafenib: 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 · EPHA2 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 · 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-000052-PIP01-07-M03 (vandetanib, Treatment of medullary thyroid carcinoma): PM: decision on the application for modification of an agreed PIP, 30 Nov 2013; compliance positive 20 Jun 2014Rule: 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/3/05/344 withdrawn 24 Jan 2006: Treatment of medullary thyroid carcinomaRule: 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 · Caprelsa: authorised since 16 Feb 2012; Stivarga: authorised since 26 Aug 2013; Zactima: application withdrawnRule: 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: no · FDA's table lists no pediatric approval of vandetanib, regorafenibRule: 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 · 24 interventional studies of vandetanib, regorafenib include patients under 18; 7 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 3 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.