{"entity":{"id":"tiragolumab","kind":"drug","name":"Tiragolumab","aka":[],"tldr":"An immune-brake blocker that looked excellent in a phase 2 lung cancer trial and then failed every phase 3.","summary":"CITYSCAPE (phase 2, 2020) showed tiragolumab plus atezolizumab roughly doubled response rate in PD-L1-high NSCLC. Phase 3 SKYSCRAPER-01 (PD-L1-high NSCLC) missed PFS and OS; SKYSCRAPER-02 (extensive-stage SCLC) was negative; SKYSCRAPER-06 (non-squamous NSCLC) was worse than control. Roche discontinued most of the programme in 2024 and 2025. Other anti-TIGIT antibodies (domvanalimab, ociperlimab) showed no clearer benefit.\n\nLesson: a small randomised phase 2 with a surrogate endpoint in a selected population can mislead; redundancy between checkpoints means blocking a second one does not necessarily add to PD-1/PD-L1 blockade.","status":"negative","asOf":"2026-09-06","links":[{"label":"Roche SKYSCRAPER-01 final analysis (2024)","url":"https://www.roche.com/media/releases/med-cor-2024-11-26"}],"tags":["failure","lesson:phase-2-mirage"],"related":["tigit-plus-pd1-caution"],"cancers":["nsclc","sclc"],"sections":[],"technologies":["checkpoint-inhibitor","tigit-blockade"],"targets":["tigit","pdl1"],"drugs":["atezolizumab"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05904886","nct05009069","nct05805501","nct04524871","nct05645692","nct04665856"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"RG6058, MTIG7192A","modality":"Monoclonal antibody (anti-TIGIT)","mechanism":"IgG1 anti-TIGIT with intact Fc; blocks TIGIT-PVR interaction on T and NK cells.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/tiragolumab/","neighbours":{"pairing":[{"id":"tigit-plus-pd1-caution","kind":"pairing","name":"Caution: TIGIT + PD-(L)1 blockade","route":"/pairings/tigit-plus-pd1-caution/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"tigit-blockade","kind":"technology","name":"TIGIT blockade","route":"/technologies/tigit-blockade/"}],"target":[{"id":"pvr","kind":"target","name":"CD155 (PVR)","route":"/targets/pvr/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"},{"id":"tigit","kind":"target","name":"TIGIT","route":"/targets/tigit/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"trial":[{"id":"nct05904886","kind":"trial","name":"A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocell","route":"/trials/nct05904886/"},{"id":"nct05645692","kind":"trial","name":"A Study Evaluating Different Immunotherapies (LAG-3 and PD-1 With or Without TIGIT, Compared to PD-L1 Alone) in Participants With Untreated Locally Advanced Metastatic Urothelial Cancer","route":"/trials/nct05645692/"},{"id":"nct04524871","kind":"trial","name":"A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Li","route":"/trials/nct04524871/"},{"id":"nct05009069","kind":"trial","name":"A Study of Atezolizumab With or Without Tiragolumab Following Neoadjuvant Chemoradiotherapy in Participants With Locally Advanced Rectal Cancer","route":"/trials/nct05009069/"},{"id":"nct05805501","kind":"trial","name":"A Study of Immune Checkpoint Inhibitor Combinations With Axitinib in Participants With Untreated Locally Advanced Unresectable or Metastatic Renal Cel","route":"/trials/nct05805501/"},{"id":"nct06342037","kind":"trial","name":"NOvel Immunotherapy Strategies for Advanced Triple Negative Breast Cancer (TNBC) Patients: TONIC-3 Trial","route":"/trials/nct06342037/"},{"id":"nct04665856","kind":"trial","name":"Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Participants With Untreated Extensive-Stage Small Cell Lung Cancer","route":"/trials/nct04665856/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-negative-results","kind":"bottleneck","name":"Failures are hidden","route":"/bottlenecks/b-negative-results/"}],"idea":[{"id":"idea-fund-shelved-asset-escrow","kind":"idea","name":"Automatic offer of shelved cancer assets to non-profits after two years","route":"/ideas/idea-fund-shelved-asset-escrow/"},{"id":"idea-tr2-contribution-of-components-mandate","kind":"idea","name":"No accelerated approval for a combination without proof each part contributes","route":"/ideas/idea-tr2-contribution-of-components-mandate/"}],"pathway":[{"id":"nk-cell-recognition","kind":"pathway","name":"NK-cell recognition: missing self & stress ligands","route":"/pathways/nk-cell-recognition/"},{"id":"t-cell-exhaustion","kind":"pathway","name":"T-cell exhaustion","route":"/pathways/t-cell-exhaustion/"}]}}