# Caution: TIGIT + PD-(L)1 blockade

Source: https://onco.cc/pairings/tigit-plus-pd1-caution/  
OnCo record `tigit-plus-pd1-caution` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Pairing
- Last checked: 2026-09-04
- Pairs: TIGIT + Immune checkpoint inhibitors
- Type: caution
- Rationale: Unclear; Fc-effector requirements, patient selection, and redundancy with PD-1 are proposed explanations.
- Evidence: Multiple negative phase 3.

## Sources

- SKYSCRAPER-01: tiragolumab plus atezolizumab in previously untreated PD-L1-high non-small-cell lung cancer, phase 3 (Journal of Clinical Oncology 2026): https://doi.org/10.1200/JCO-25-02777
- CITYSCAPE: tiragolumab plus atezolizumab versus placebo plus atezolizumab as first-line treatment for PD-L1-selected NSCLC, phase 2 (Lancet Oncology 2022): https://doi.org/10.1016/S1470-2045(22)00226-1

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/)
- targets: [PD-L1](https://onco.cc/targets/pdl1/), [TIGIT](https://onco.cc/targets/tigit/)
- key papers: [SKYSCRAPER-01: Tiragolumab in Combination With Atezolizumab in Previously Untreated PD-L1-High, Locally Advanced, Unresectable or Metastatic Non-Small Cell Lung Cancer](https://onco.cc/key-papers/paper-peters-j-clin-oncol/), [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](https://onco.cc/key-papers/paper-cho-lancet-oncol/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Tiragolumab](https://onco.cc/drugs/tiragolumab/)
- ideas: [No accelerated approval for a combination without proof each part contributes](https://onco.cc/ideas/idea-tr2-contribution-of-components-mandate/)

---
JSON: https://onco.cc/api/v1/entities/tigit-plus-pd1-caution.json