tiragolumab (RG6058) / Roche - LARVOL DELTA

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. (PubMed, J Clin Oncol) - "Tiragolumab did not provide additional benefit over atezolizumab and CE in untreated ES-SCLC. The combination was well tolerated with no new safety signals."

Combination therapy • Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

SKYSCRAPER-05: A Phase 2 Study of Perioperative Tiragolumab Plus Atezolizumab, With or Without Platinum-Based Chemotherapy, in Patients With Previously Untreated, Locally Advanced, Resectable, Stage II‒IIIB NSCLC. (PubMed, JTO Clin Res Rep) - P2 | "AEs led to surgical delays in 2 patients and treatment discontinuation in 14 patients (34.1%, all in Cohort B). Perioperative tiragolumab combined with atezolizumab ± chemotherapy proved to be surgically feasible, with acceptable MPR rates and a safety profile aligned with expectations for resectable, locally advanced NSCLC."

Clinical • Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

NeoACTIVATE arm C: Phase II trial of neoadjuvant atezolizumab and tiragolumab for high-risk operable stage III melanoma. (ASCO 2025) - P2 | "Among patients with high-risk resectable stage III melanoma, neoadjuvant atezo/tira was a promising regimen with a favorable safety profile and warrants further study. Identification of predictive biomarkers will allow for optimization of neoadjuvant therapy for individual patients. Pathologic response."

Clinical • IO biomarker • P2 data • Melanoma • Oncology • Solid Tumor • TIGIT

Randomized Parallel-Group Phase II Study (NEOTERIC) of Atezolizumab With or Without Tiragolumab After Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer. (PubMed, J Clin Oncol) - "In patients with LARC, Atezo + Tira after nCRT statistically improved the pCR rate compared with historical controls, with an acceptable safety profile."

Journal • P2 data • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor

SKYSCRAPER-01: A phase III, randomized trial of tiragolumab (tira) + atezolizumab (atezo) versus placebo (pbo) + atezo in patients (pts) with previously-untreated PD-L1-high, locally advanced unresectable/metastatic NSCLC (AACR 2025) - P3 | "The primary endpoints of INV-PFS and OS were not met in the SKYSCRAPER-01 study. Numerical improvements in both PFS and OS with tira + atezo versus pbo + atezo suggest potential antitumor activity of TIGIT targeting in NSCLC.TablePAS (TPS ≥50% per 22C3 assay)Tira + atezo(n=262)Pbo + atezo(n=259)Median PFS, months (95% CI)*†7.0 (5.6, 9.8)5.6 (4.4, 7.0)HR (95% CI); p-value0.78 (0.63, 0.97); p=0.02Median OS, months (95% CI)*†23.1 (17.7, 28.8)16.9 (14.6, 23.1)HR (95% CI); p-value0.87 (0.71, 1.08); p=0.22ORR, %*45.835.1Median DOR, months (95% CI)*18.0 (13.6, 24.4)14.6 (9.7, 18.6)SAS (TC ≥50% per SP263 assay)Tira + atezo(n=211)Pbo + atezo(n=209)Median OS, months (95% CI)*24.6 (17.9, 32.0)20.6 (16.6, 29.3)HR (95% CI)0.93 (0.73, 1.18)Safety evaluable set‡Tira + atezo(n=267)Pbo + atezo(n=263)Any grade AEs, %95.991.3Grade 3-4 AEs, %41.233.8Grade 5 AEs, %10.99.9Treatment-related grade 5 AEs, %1.50.8AEs leading to treatment withdrawal, %16.16.5Any grade AESIs, %70.050.6*PFS..."

Clinical • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • PD-L1 • TIGIT

SKYSCRAPER-07: A Study of Atezolizumab With or Without Tiragolumab in Participants With Unresectable Esophageal Squamous Cell Carcinoma Whose Cancers Have Not Progressed Following Definitive Concurrent Chemoradiotherapy (clinicaltrials.gov) - P3 | N=760 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | Trial completion date: Mar 2027 ➔ Jul 2026 | Trial primary completion date: Mar 2027 ➔ Jul 2026

Trial completion • Trial completion date • Trial primary completion date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver) (clinicaltrials.gov) - P1/2 | N=518 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Liver Cancer • Oncology • Solid Tumor • PD-L1

Results from the MORPHEUS-liver study: Phase Ib/II randomized evaluation of tiragolumab (tira) in combination with atezolizumab (atezo) and bevacizumab (bev) in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC). (ASCO 2023) - P1/2 | "Background: Atezo + bev is the current first-line standard of care for uHCC based on the IMbrave150 study, which demonstrated superior overall survival, progression-free survival (PFS), and objective response rate (ORR) vs sorafenib (Finn, et al. The addition of tira to atezo + bev resulted in higher ORR and longer PFS compared with atezo + bev, and no new safety signals were identified. These data suggest that tira + atezo + bev may be a promising novel first-line treatment option for patients with uHCC, and support further study in this setting. Clinical trial information: NCT04524871."

Clinical • Combination therapy • Metastases • P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Immune Modulation • Oncology • Solid Tumor • TIGIT

Neoadjuvant and adjuvant tiragolumab plus atezolizumab in PD-L1-positive oral cavity squamous cell carcinoma (ESMO 2026) - No abstract available

Clinical • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Perioperative Tiragolumab, Atezolizumab and Chemotherapy in resectable non-small cell lung cancer - first clinical experience from the phase II NeoTRACK trial (DGT 2026) - "Neoadjuvant dual ICI with TIRA and ATE plus chemotherapy was feasible in terms of preoperative treatment and surgical outcomes.R0 resections were achieved in all patients, and promising pathological response rates were observed after only two treatment cycles.However, the comparatively high incidence of treatment-related toxicities, especially during the adjuvant study period, warrants further investigation.Furthermore, global anti-TIGIT strategies were also discontinued after initial negative efficacy results.These findings underscore the need for further discussion of the TIGIT pathway in future perioperative treatment strategies."

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TIGIT

SKYSCRAPER-09: Phase II, randomised study of tiragolumab (tira) + atezolizumab (atezo) and atezo + placebo (pbo) as first-line (1L) treatment in patients (pts) with recurrent/metastatic PD-L1+ squamous cell carcinoma of the head and neck (R/M SCCHN) (ESMO 2025) - P2 | "Background The current standard of care for R/M PD-L1+ SCCHN is pembrolizumab. A numerical improvement in OS was observed with tira + atezo vs atezo + pbo; this was driven by the PD-L1-high subgroup and may be clinically meaningful. Table: 1348MO PD-L1+ (TAP ≥5%)* PD-L1-high (TAP ≥20%) Tira + atezo (n=80) Atezo + pbo (n=39) Tira + atezo (n=41) Atezo + pbo (n=22) ORR, † n (%) [95% CI] 17 (21.3) [13.2, 32.1] 6 (15.4) [6.4, 31.2] 12 (29.3) [16.7, 45.7] 3 (13.6) [3.6, 36.0] Median PFS, m (95% CI) 4.1 (2.9, 7.0) 3.0 (1.5, 7.1) 5.8 (2.8, 9.6) 4.0 (2.7, 9.0) Median OS, m (95% CI) 16.2 (12.7, 19.9) 13.6 (8.8, 18.9) 22.7 (16.9, NE) 10.0 (6.8, 18.7) *Intent-to-treat population † Investigator-assessed CI, confidence interval; NE, not estimable"

Clinical • Metastases • P2 data • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

SKYSCRAPER-08: A phase III, randomized, double-blind, placebo-controlled study of first-line (1L) tiragolumab (tira) + atezolizumab (atezo) and chemotherapy (CT) in patients (pts) with esophageal squamous cell carcinoma (ESCC). (ASCO-GI 2024) - P3 | " Eligible pts (confirmed LA or R/M ESCC; ECOG PS 0–1; no prior systemic tx) were randomized 1:1 to receive tira 600mg + atezo 1200mg + CT (paclitaxel 175mg/m2 + cisplatin 60–80mg/m2, local standard of care) or placebo + CT on Day 1 of each 21-day cycle (cycles 1–6); followed by tira + atezo or placebo maintenance until loss of clinical benefit/unacceptable toxicity. The study met both primary endpoints of IRF-assessed PFS and OS, demonstrating statistically significant and clinically meaningful improvements in PFS and OS for tira + atezo + CT over placebo + CT. Generally consistent benefit was observed across subgroups, including PD-L1 status. The safety profile was consistent with the known risks of the individual tx."

Clinical • P3 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology • TIGIT

Anti-TIGIT antibody tiragolumab leverages myeloid cells and regulatory T cells to improve PD-L1 checkpoint blockade (AACR 2023) - P2 | "In a randomized double-blind phase 2 clinical trial in non-small cell lung cancer (NSCLC), tiragolumab + atezolizumab (anti-PD-L1) combination treatment demonstrated significant improvement relative to atezolizumab alone. These findings reveal that FcR engagement is one of several distinct mechanisms by which tiragolumab unleashes antitumor immune responses, and inform further clinical development of anti-TIGIT therapies."

Checkpoint block • Checkpoint inhibition • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • PTPRC • TIGIT

Tiragolumab Plus Atezolizumab and Chemotherapy for Advanced Nonsquamous Non-Small Cell Lung Cancer: The Phase 3 SKYSCRAPER-06 Randomized Clinical Trial. (PubMed, JAMA Oncol) - P2/3 | "Patients were randomized 1:1 to receive either tiragolumab, 600 mg, plus atezolizumab, 1200 mg, plus chemotherapy (pemetrexed, 500 mg/m2, and carboplatin [area under the curve 5], or cisplatin, 75 mg/m2) or placebo plus pembrolizumab, 200 mg, plus chemotherapy via intravenous infusion on day 1 of each 21-day cycle until disease progression, loss of clinical benefit, unacceptable toxic effect, or withdrawal of consent. In the phase 3 SKYSCRAPER-06 randomized clinical trial, the primary end points were not met and the study has been terminated. ClinicalTrials.gov Identifier: NCT04619797."

Clinical • Journal • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells. (PubMed, Nature) - P2 | "Tiragolumab, an anti-TIGIT antibody with an active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: NCT03563716 ) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone1. In mouse tumour models, tiragolumab surrogate antibodies inflamed tumour-associated macrophages, monocytes and dendritic cells through Fcγ receptors (FcγR), in turn driving anti-tumour CD8+ T cells from an exhausted effector-like state to a more memory-like state. These results reveal a mechanism of action through which TIGIT checkpoint inhibitors can remodel immunosuppressive tumour microenvironments, and suggest that FcγR engagement is an important consideration in anti-TIGIT antibody development."

Journal • Oncology • CD8 • TIGIT

SKYSCRAPER-01: Tiragolumab in Combination With Atezolizumab in Previously Untreated PD-L1-High, Locally Advanced, Unresectable or Metastatic Non-Small Cell Lung Cancer. (PubMed, J Clin Oncol) - "Tiragolumab plus atezolizumab did not demonstrate a statistically significant INV-PFS or OS benefit over atezolizumab in patients with previously untreated PD-L1-high NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Tiragolumab in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (MORPHEUS-Liver): a randomised, open-label, phase 1b-2, study. (PubMed, Lancet Oncol) - P1/2 | "This signal-seeking study suggests that the addition of tiragolumab to atezolizumab and bevacizumab might be more clinically active than atezolizumab plus bevacizumab alone in unresectable hepatocellular carcinoma. Based on these data, further study of combination tiragolumab plus atezolizumab plus bevacizumab is warranted."

Journal • P1/2 data • Cardiovascular • Cholestasis • Gastroenterology • Gastrointestinal Disorder • Hepatocellular Cancer • Hepatology • Hypertension • Musculoskeletal Pain • Oncology • Pruritus • Renal Disease • Solid Tumor • TIGIT

Tiragolumab Plus Atezolizumab and Bevacizumab in Targeted Therapy-Refractory, Immune Checkpoint Blockade-Naive, Advanced EGFR-Mutated NSCLC (IASLC-TTLC 2026) - P2 | "One patient was started on osimertinib monotherapy following disease progression on docetaxel plus ramucirumab after progression on trial therapy and developed hepatic failure resulting in death (grade 5). Accrual was halted early following termination of tiragolumab development. Interim analysis demonstrated minimal clinical efficacy of dual ICB with VEGF inhibition in TT- refractory, ICB-naïve EGFRm NSCLC. These findings suggest this combination is unlikely to represent an effective therapeutic strategy in this population."

Checkpoint block • Checkpoint inhibition • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR • TIGIT

SKYSCAPPER-02C: Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Participants With Untreated Extensive-Stage Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=123 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | Trial completion date: Jun 2026 ➔ Nov 2025

Trial completion • Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma (clinicaltrials.gov) - P1/2 | N=62 | Terminated | Sponsor: Hoffmann-La Roche | Completed ➔ Terminated; Study was closed early as the sponsor decided not to continue development of certain treatment combinations.

Trial termination • Hepatocellular Cancer • Oncology • Solid Tumor

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. (PubMed, Lancet Oncol) - P2 | "Tiragolumab plus atezolizumab showed a clinically meaningful improvement in objective response rate and progression-free survival compared with placebo plus atezolizumab in patients with chemotherapy-naive, PD-L1-positive, recurrent or metastatic NSCLC. Tiragolumab plus atezolizumab was well tolerated, with a safety profile generally similar to that of atezolizumab alone. These findings demonstrate that tiragolumab plus atezolizumab is a promising immunotherapy combination for the treatment of previously untreated, locally advanced unresectable or metastatic NSCLC."

Journal • P2 data • Immune Modulation • Infectious Disease • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1 • TIGIT

SKYSCRAPER-03: Phase III, open-label, randomised study of atezolizumab (atezo) + tiragolumab (tira) vs durvalumab (durva) in locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC) after platinum-based concurrent chemoradiation (cCRT) (ESMO 2025) - P3 | "Conclusions Atezo + tira did not offer additional benefit over durva in pts with unresectable, stage III NSCLC. The safety profile of atezo + tira was consistent with prior observations."

Clinical • IO biomarker • Late-breaking abstract • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

IMbrave152/SKYSCRAPER-14: A phase III study of first-line tiragolumab (tira) + atezolizumab (atezo) + bevacizumab (bev) vs placebo (pbo) + atezo + bev for patients (pts) with untreated locally advanced or metastatic hepatocellular carcinoma (HCC) (ESMO 2025) - P3 | "OS data are not expected to reach statistical significance. The study has been unblinded and long-term survival follow-up is ongoing."

Clinical • Late-breaking abstract • Metastases • P3 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • TIGIT

Tiragolumab Plus Atezolizumab and Bevacizumab in Immunotherapy-Refractory, PD-L1-Positive, Advanced NSCLC (IASLC-WCLC 2026) - P2 | "Responses observed in patients with KEAP1-mutated NSCLC suggest a potential signal of benefit that warrants further investigation. Ongoing blood and tissue correlative analyses will explore biomarkers suggestive of benefit observed with this regimen."

IO biomarker • Metastases • Hypertension • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Respiratory Diseases • Solid Tumor • KEAP1 • KRAS • SMARCA4 • STK11 • TIGIT

SKYSCRAPER-02: Primary results of a phase III, randomized, double-blind, placebo-controlled study of atezolizumab (atezo) + carboplatin + etoposide (CE) with or without tiragolumab (tira) in patients (pts) with untreated extensive-stage small cell lung cancer (ES-SCLC). (ASCO 2022) - P3 | "The addition of tira to atezo + CE did not provide benefit over atezo + CE in pts with untreated ES-SCLC with or without BM. The combination was well tolerated, and no new safety signals were identified. The study will continue to planned final OS analysis."

Clinical • Late-breaking abstract • P3 data • Immune Modulation • Inflammation • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • TIGIT