Investigational Drug
Tiragolumab
HealthScout AI Analysis
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Overview
Tiragolumab (MTIG7192A, RG6058, RO7092284) is a human IgG1/k monoclonal antibody that targets the inhibitory receptor TIGIT. It has been studied mostly in combination with the PD‑L1 inhibitor atezolizumab across multiple tumor types. Early randomized phase 2 data in PD‑L1–positive NSCLC suggested activity, but several subsequent phase 3 trials in lung cancer did not meet primary endpoints. Positive phase 3 results have been reported in first‑line esophageal squamous cell carcinoma (ESCC) with chemo‑immunotherapy. (pubmed.ncbi.nlm.nih.gov)
Mechanism of action
- Target: TIGIT, an inhibitory receptor on activated T cells and NK cells; major ligand CD155 (PVR). Tiragolumab blocks TIGIT–CD155/CD112 interactions, aiming to restore antitumor immunity. (dctd.cancer.gov)
- Antibody features: Fc‑competent IgG1; emerging translational work indicates FcγR engagement may activate myeloid cells and modulate Treg biology, potentially enhancing PD‑L1 blockade. (pubmed.ncbi.nlm.nih.gov)
Efficacy
Non–small cell lung cancer (NSCLC)
- Phase 2 (CITYSCAPE): In PD‑L1–positive, treatment‑naive metastatic NSCLC, tiragolumab + atezolizumab improved outcomes vs atezolizumab alone. Reported ORR 38.8% vs 20.6% (intent‑to‑treat), with pronounced effect in PD‑L1 TPS ≥50% (ORR 69% vs 24%); PFS HR 0.62 (overall) and 0.29 (PD‑L1‑high). (pubmed.ncbi.nlm.nih.gov)
- Phase 3 (SKYSCRAPER‑01, PD‑L1‑high): Did not meet the primary endpoint of overall survival at the final analysis vs atezolizumab alone; detailed data pending presentation. (reuters.com)
Small‑cell lung cancer (ES‑SCLC) - Phase 3 (SKYSCRAPER‑02): Adding tiragolumab to atezolizumab + carboplatin/etoposide did not improve PFS (median 5.4 vs 5.6 months; HR 1.11) or OS (median 13.1 months both arms; HR 1.14). (pubmed.ncbi.nlm.nih.gov)
Non‑squamous NSCLC vs pembrolizumab‑chemo - Phase 2/3 (SKYSCRAPER‑06): The tiragolumab + atezolizumab + chemotherapy arm showed reduced efficacy vs pembrolizumab + chemotherapy; primary PFS and interim OS endpoints were not met; trial discontinued. (businesswire.com)
Esophageal squamous cell carcinoma (ESCC) - Phase 3 (SKYSCRAPER‑08): First‑line tiragolumab + atezolizumab + chemotherapy improved PFS (IRF median 6.2 vs 5.4 months; HR 0.56; p<0.0001), OS (median 15.7 vs 11.1 months; HR 0.70; p=0.0024), and ORR (59.7% vs 45.5%). (ascopubs.org)
Head and neck cancer - A dedicated randomized phase 2 of atezolizumab ± tiragolumab in PD‑L1–positive recurrent/metastatic HNSCC is ongoing/registered; peer‑reviewed efficacy results were not identified. (clinicaltrials.ucbraid.org)
Safety
Across randomized studies, tiragolumab combinations showed toxicity profiles generally consistent with PD‑L1 inhibitors and background chemotherapy, with no new safety signals noted.
- ES‑SCLC (SKYSCRAPER‑02): Immune‑mediated AEs in 54.4% vs 49.2% (grade 3/4: 7.9% vs 7.7%); treatment withdrawal 8.4% vs 9.3% (tiragolumab vs control). (pubmed.ncbi.nlm.nih.gov)
- ESCC (SKYSCRAPER‑08): Grade 3/4 treatment‑related AEs 59.6% vs 56.4%; grade 5 2.6% vs 0.9% (tiragolumab combo vs control). (ascopubs.org)
- PD‑L1‑high NSCLC (SKYSCRAPER‑01): Sponsor reports indicate no new safety signals at final analysis. (reuters.com)
Further reading
- CITYSCAPE phase 2 NSCLC primary and follow‑up analyses (Lancet Oncology 2022). (pubmed.ncbi.nlm.nih.gov)
- SKYSCRAPER‑02 phase 3 ES‑SCLC (J Clin Oncol 2024, full text). (ascopubs.org)
- SKYSCRAPER‑08 phase 3 ESCC (ASCO GI 2024 abstract). (ascopubs.org)
- Mechanistic study on Fc‑dependent myeloid/Treg modulation by tiragolumab (Nat Immunol‑adjacent/PMID 38418879; J Immunol 2024 abstract). (pubmed.ncbi.nlm.nih.gov)
- NCI drug page for tiragolumab (target and mechanism overview). (dctd.cancer.gov)
- Updates on SKYSCRAPER‑01 OS outcome and program changes. (reuters.com)
Notes: As of October 7, 2025, phase 3 lung cancer trials with tiragolumab (SKYSCRAPER‑01 and ‑06) have not demonstrated survival benefit, while SKYSCRAPER‑08 in ESCC reported statistically significant improvements in both PFS and OS. Pending detailed publications may further clarify benefit–risk in specific subgroups. (reuters.com)
Last updated: Oct 2025
Active trials using Tiragolumab
Found 5 active trials using this drug:
HealthScout AI summary: This trial enrolls adults with microsatellite stable metastatic colorectal cancer who have progressed after at least two prior therapies and have at least two lesions, testing combination therapy with atezolizumab (anti-PD-L1), tiragolumab (anti-TIGIT), and stereotactic body radiation therapy. Patients must be immunotherapy-naïve and fit (ECOG 0-1), with one lesion suitable for SBRT and another measurable for response.
ClinicalTrials.gov ID: NCT06603818
HealthScout AI summary: This trial enrolls adults with advanced non-squamous NSCLC who have progressed after anti-PD(L)1 therapy or, for EGFR-mutant patients, after EGFR-targeted therapy, to receive tiragolumab (a TIGIT inhibitor), atezolizumab, and bevacizumab. Key eligibility includes ECOG 0-2, no known driver mutations (except EGFR-mutant cohort), and no untreated/symptomatic CNS metastases.
ClinicalTrials.gov ID: NCT04958811
HealthScout AI summary: Adults with previously treated metastatic colorectal adenocarcinoma whose tumors harbor specific biomarkers are assigned to various arms testing targeted agents—including the PI3Kα inhibitor inavolisib, TIGIT inhibitor tiragolumab (with anti–PD-L1 and bevacizumab), CDK7 inhibitor SY-5609, and KRAS G12C inhibitor divarasib (with chemotherapy or EGFR/VEGF antibodies)—according to their molecular profile.
ClinicalTrials.gov ID: NCT04929223
HealthScout AI summary: Biomarker-driven platform for adults with recurrent/persistent endometrial carcinoma after 1–2 prior lines, assigning patients by FoundationOne CDx to targeted doublets with or without the PD‑L1 inhibitor atezolizumab. Active cohorts include atezolizumab plus talazoparib for high genomic LOH, atezolizumab plus anti‑TIGIT tiragolumab for MSI‑H/high TMB tumors, inavolisib (PI3Kα inhibitor) plus letrozole for PIK3CA‑mutant tumors without PTEN/AKT1 alterations, and giredestrant (oral SERD) plus abemaciclib for ER‑positive, RB1‑intact disease.
ClinicalTrials.gov ID: NCT04486352
HealthScout AI summary: Adults with unresectable, locally advanced or metastatic HCC eligible for first-line therapy (ECOG 0–1, Child-Pugh A; exclusions include prior systemic therapy and high-risk portal hypertension) are randomized to atezolizumab/bevacizumab versus multiple immunotherapy-based combinations. Experimental arms include additions such as anti-TIGIT (tiragolumab), anti–IL-6R (tocilizumab), PPARα antagonist (TPST-1120/amezalpat), PD-1/LAG-3 bispecific (tobemstomig), masked anti–CTLA-4 (ADG126/muzastotug), anti-LILRB2 myeloid checkpoint (IO-108), or HIF-2α inhibitor (NKT2152/imdatifan), with adaptive crossover allowed after loss of benefit or toxicity.
ClinicalTrials.gov ID: NCT04524871
