{"entity":{"id":"tigit-plus-pd1-caution","kind":"pairing","name":"Caution: TIGIT + PD-(L)1 blockade","aka":[],"tldr":"Adding a TIGIT blocker to PD-1/PD-L1 blockade looked good in phase 2 and then failed repeatedly in phase 3.","summary":"This caution pairing concerns adding a TIGIT blocker to Immune checkpoint inhibitors against PD-1 or PD-L1, a combination that looked promising in phase 2 and then failed repeatedly in phase 3. SKYSCRAPER-01 (Tiragolumab plus atezolizumab in Non-small-cell lung cancer), SKYSCRAPER-02 in Small-cell lung cancer and other trials were negative, the phase 2 signals did not reproduce, and Roche and others discontinued most TIGIT programmes in 2024-25. The reason for failure is unclear: Fc-effector requirements, patient selection and redundancy with PD-1 are the proposed explanations. The episode is cited in the idea that no accelerated approval should be granted for a combination without proof that each part contributes, and it is linked from the Tiragolumab and TIGIT entries.","asOf":"2026-09-04","links":[{"label":"SKYSCRAPER-01: tiragolumab plus atezolizumab in previously untreated PD-L1-high non-small-cell lung cancer, phase 3 (Journal of Clinical Oncology 2026)","url":"https://doi.org/10.1200/JCO-25-02777"},{"label":"CITYSCAPE: tiragolumab plus atezolizumab versus placebo plus atezolizumab as first-line treatment for PD-L1-selected NSCLC, phase 2 (Lancet Oncology 2022)","url":"https://doi.org/10.1016/S1470-2045(22)00226-1"}],"tags":[],"related":[],"cancers":["nsclc","sclc"],"sections":[],"technologies":[],"targets":["tigit","pdl1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cho-lancet-oncol","paper-peters-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"a":"tigit","b":"checkpoint-inhibitor","rationale":"Unclear; Fc-effector requirements, patient selection, and redundancy with PD-1 are proposed explanations.","evidence":"Multiple negative phase 3.","pairingType":"caution"},"route":"/pairings/tigit-plus-pd1-caution/","neighbours":{"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/"}],"target":[{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"},{"id":"tigit","kind":"target","name":"TIGIT","route":"/targets/tigit/"}],"paper":[{"id":"paper-peters-j-clin-oncol","kind":"paper","name":"SKYSCRAPER-01: Tiragolumab in Combination With Atezolizumab in Previously Untreated PD-L1-High, Locally Advanced, Unresectable or Metastatic Non-Small Cell Lung Cancer","route":"/key-papers/paper-peters-j-clin-oncol/"},{"id":"paper-cho-lancet-oncol","kind":"paper","name":"Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study","route":"/key-papers/paper-cho-lancet-oncol/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"tiragolumab","kind":"drug","name":"Tiragolumab","route":"/drugs/tiragolumab/"}],"idea":[{"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/"}]}}