TIGIT T cell immunoreceptor with Ig and ITIM domains
ENSG00000181847 · protein coding · Open Targets profile
Inhibitory receptor that plays a role in the modulation of immune responses. Suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells (PubMed:19011627). Upon binding to its ligands PVR/CD155 or NECTIN2/CD112, which are expressed on antigen-presenting cells, sends inhibitory signals to the T-cell or NK cell. Mechanistically, interaction with ligand leads to phosphorylation of the cytoplasmic tail by Src family tyrosine kinases such as FYN or LCK, allowing subsequent binding to adapter GRB2 and SHIP1/INPP5D. In turn, inhibits PI3K and MAPK signaling cascades (PubMed:23154388). In addition, associates with beta-arrestin-2/ARRB2 to recruit SHIP1/INPP5D that suppresses autoubiquitination of TRAF6 and subsequently inhibits NF- kappa-B signaling pathway (PubMed:24817116). Also acts as a receptor for NECTIN4 to inhibit NK cell cytotoxicity (PubMed:32503945). {ECO:0000269|PubMed:19011627, ECO:0000269|PubMed:23154388, ECO:0000269|PubMed:24817116, ECO:0000269|PubMed:32503945}.
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 Withdrawn means the drug was pulled from the market or from development.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
- Antibody
- Advanced Clinical, UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- Other modalities
- Phase 1 Clinical
gnomAD loss of function constraint: o/e 0.562309980392456 (upper bound 0.9307500123977661). 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 116 registry trials, updated in the last three years, of the most advanced drugs against TIGIT (ociperlimab, tiragolumab, domvanalimab, vibostolimab, etigilimab), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Alexander SpiraVirginia Cancer Specialists Research Institute · 1 of 1 trials Phase 2+
- Chia-Hsien ChengEmployee · 1 of 1 trials Phase 2+
- Daniel MorgenszternWashington University School of Medicine · 1 of 1 trials Phase 2+
- David HsiehAssistant Professor · 1 of 1 trials Phase 2+
- David ThomasOmico; UNSW Sydney · 1 of 1 trials Phase 2+
- Derk JA de GrootUniversity Medical Center Groningen · 1 of 1 trials Phase 2+
- Emma HollidayM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
- Evanthia GalanisAlliance Foundation Trials, LLC. · 1 of 1 trials Phase 2+
- Florian EichhornUniversity Hospital Heidelberg · 1 of 1 trials Phase 2+
- François-Clément BidardInstitut Curie · 1 of 1 trials Phase 2+
- George AnsstasWashington University School of Medicine · 1 of 1 trials Phase 2+
- Hannah RobinsonUniversity of Colorado, Denver · 1 of 1 trials Phase 2+
- Helen RossRush University · 1 of 1 trials Phase 2+
- Hidehito HorinouchiNational Cancer Center Hospital · 1 of 1 trials Phase 2+
- Ignacio DuranHospital Universitario Marqués de Valdecilla · 1 of 1 trials Phase 2+
Registry trials of ociperlimab, tiragolumab, domvanalimab, vibostolimab, etigilimab 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; 43 of 108 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. 8 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
33 trials of drugs against TIGIT were stopped early
Terminated, withdrawn and suspended interventional trials of ociperlimab, tiragolumab, domvanalimab, vibostolimab, etigilimab, ASP-8374, IBI-939, 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 33.
- terminated · 2026-09-17 · Merck Sharp & Dohme LLC · Pembrolizumab/Vibostolimab“Business Reasons”
- terminated · 2026-09-15 · Hoffmann-La Roche · Tiragolumab“Study was closed early as the sponsor decided not to continue development of certain treatment combinations.”
- terminated · 2026-09-11 · Merck Sharp & Dohme LLC · Pembrolizumab/Vibostolimab“MK-7684A-007 was terminated early due to futility. A non-submission CSR, not intended to support any registration, was issued; therefore, an abbreviated CSR was generated.”
- terminated · 2026-09-10 · Merck Sharp & Dohme LLC · Pembrolizumab/Vibostolimab“Business Reason”
- terminated · 2026-08-31 · Merck Sharp & Dohme LLC · Pembrolizumab/vibostolimab coformulation“Business Reasons”
- suspended · 2026-08-21 · Royal Marsden NHS Foundation Trust · Combination zimberelimab + domvanalimab“Gilead's ongoing evaluation of the wider Zimberelimab and Domvanalimab programme, following the outcomes of the STAR-221 study and the discontinuation of EDGE-Gastric studies. No safety concerns have been identified in relation to ZODIAC.”
- terminated · 2026-08-03 · Hoffmann-La Roche · Tiragolumab“The study was closed because the sponsor decided not to continue the development of certain treatment combinations.”
- terminated · 2026-08-03 · Hoffmann-La Roche · Tiragolumab“Study was closed early as the sponsor decided not to continue development of certain treatment combinations.”
- terminated · 2026-06-10 · Hoffmann-La Roche · Tiragolumab“Decision to terminate study was driven by results from preceding tiragolumab study (SKYSCRAPER-06;NCT04619797) \& sponsor's strategic priorities, not due to safety risks or quality reasons for any of molecules/combinations investigated in this study.”
- suspended · 2026-06-04 · James Cleary, MD, PhD · DOMVANALIMAB“Efficacy concerns.”
- terminated · 2026-05-12 · BeiGene · Ociperlimab“This decision was conducted by the sponsor based on lack of efficacy and not driven by safety concerns.”
- terminated · 2026-05-12 · Hoffmann-La Roche · Tiragolumab“Study was closed early as the sponsor decided not to continue development of certain treatment combinations.”
- withdrawn · 2026-05-01 · MedSIR · Domvanalimab (DOM)“The interim analysis of the STAR-221 study showed that the domvanalimab combination did not improve overall survival compared to standard of care. No new relevant safety concerns were identified.”
- terminated · 2026-04-15 · Hoffmann-La Roche · Tiragolumab“Study was closed early as the sponsor decided not to continue development of certain treatment combinations.”
- withdrawn · 2026-03-23 · Gustave Roussy, Cancer Campus, Grand Paris · Tiragolumab 600 mg IV“Roche stopped thr peoduction of one of the study product.”
- terminated · 2026-03-11 · Hoffmann-La Roche · Tiragolumab“Study was terminated as data became available from Phase 3 trials of perioperative regimens combining chemotherapy with immunotherapy showing improved efficacy outcomes versus chemotherapy alone.”
- withdrawn · 2026-02-19 · National Cancer Institute (NCI) · Tiragolumab“The trial is closing due to findings from a related study, prompting the sponsor to discontinue development and end this study.”
- terminated · 2026-01-22 · Liza Villaruz, MD · Tiragolumab“Decision by agent provider”
- withdrawn · 2025-12-26 · Massachusetts General Hospital · Domvanalimab“The pharmaceutical company is not moving forward with this intervention due to lack of efficacy.”
- withdrawn · 2025-08-15 · M.D. Anderson Cancer Center · matched by the registry's drug synonyms“0 participants”
- withdrawn · 2025-08-05 · M.D. Anderson Cancer Center · Tiragolumab“0 participants”
- withdrawn · 2025-04-08 · Merck Sharp & Dohme LLC · Vibostolimab, Pembrolizumab/Vibostolimab“development program discontinuation”
- withdrawn · 2024-12-30 · National Cancer Institute (NCI) · Tiragolumab“Other - Protocol moved to Disapproved”
- withdrawn · 2024-12-24 · Hoffmann-La Roche · Tiragolumab“Global desprioritization decision by the sponsor.”
- terminated · 2024-11-14 · Hoffmann-La Roche · Tiragolumab“Sponsor's decision to terminate the study after Stage 1; will not proceed with Stage 2.”
Paediatric incentives and obligations for TIGIT's drugs
For ociperlimab, tiragolumab, domvanalimab, vibostolimab, etigilimab, ASP-8374, IBI-939: 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 · TIGIT 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 · EMEA-003063-PIP03-22 (vibostolimab;pembrolizumab, Treatment of melanoma): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 27 Oct 2023; EMEA-003063-PIP02-22 (vibostolimab;pembrolizumab, Treatment of Hodgkin lymphoma): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), date not given; EMEA-002721-PIP04-23 (tiragolumab, Treatment of hepatocellular carcinoma): W: decision granting a waiver in all age groups for all conditions or indications, 27 Oct 2023; EMEA-003418-PIP01-23 (tiragolumab;atezolizumab, Treatment of lung carcinoma): W: decision granting a waiver in all age groups for all conditions or indications, 8 Aug 2023; +7 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/3/25/3162 positive 9 Dec 2025: Treatment of gastric cancer; EU/3/25/3168 positive 12 Sept 2025: Treatment of oesophageal cancerRule: 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: no · EMA lists no centrally authorised medicine of ociperlimab, tiragolumab, domvanalimab, vibostolimab, etigilimab, asp-8374, ibi-939Rule: 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 ociperlimab, tiragolumab, domvanalimab, vibostolimab, etigilimab, asp-8374, ibi-939Rule: 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 · 4 interventional studies of ociperlimab, tiragolumab, domvanalimab, vibostolimab, etigilimab, asp-8374, ibi-939 include patients under 18; 2 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 7 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.