tiragolumab (RG6058) / Roche - LARVOL DELTA

A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma (clinicaltrials.gov) - P1/2 | N=62 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | Trial completion date: Sep 2028 ➔ Nov 2025

Trial completion • Trial completion date • Hepatocellular Cancer • Oncology • Solid Tumor

Atezolizumab plus tiragolumab in combination with chemoradiotherapy in localized squamous cell carcinoma of the anal canal: TIRANUS (GEMCAD-2103) trial. (ASCO-GI 2026) - P2 | "Funded by F. Hoffmann-La Roche Ltd Clinical Trial Registration Number: NCT05661188 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Combination therapy • Anal Carcinoma • Gastrointestinal Cancer • Oncology

Phase I-II trial of perioperative chemotherapy plus atezolizumab and tiragolumab in localized esophageal and gastroesophageal junction adenocarcinoma. (ASCO-GI 2026) - P2 | "Clinical Trial Registration Number: NCT03784326 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

P1/2 data • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Safety and efficacy of tiragolumab, atezolizumab and chemotherapy for early-stage or PD-L1-positive advanced triple-negative breast cancer: a phase Ib study. (PubMed, ESMO Open) - P1 | "The activity of tiragolumab-containing regimens appeared similar to that of atezolizumab plus chemotherapy in randomised phase III trials in early-stage and advanced TNBC. The safety profile of all three regimens was consistent with previous experience of similar regimens in other tumour types and with symptoms of the underlying disease."

Journal • P1 data • Breast Cancer • Hematological Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1 • TIGIT

Testing the Combination of Anti-cancer Drugs Atezolizumab and Tiragolumab in People With Advanced Stage Rare Cancers, RARE3 Trial (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial primary completion date: Oct 2026 ➔ Oct 2025

Trial primary completion date • Tumor mutational burden • Oncology • Solid Tumor • SMARCB1

An evolutionary T119R substitution in the macaque T-cell immunoreceptor TIGIT enables proteolytic shedding and reveals clinical antibody vulnerabilities. (PubMed, J Biol Chem) - "In addition, the shed ectodomain of TIGIT maintains binding to CD155 and the tested clinical anti-TIGIT antibody, tiragolumab. Given the significant anti-TIGIT failures, these unexpected findings reveal potential saturation vulnerabilities of macaque CD155 and preclinical TIGIT antibodies by soluble shedded TIGIT ectodomain, contrary to the intended mechanism of action on the lymphocyte membrane. These results caution against extrapolation and question the suitability of cynomolgus and rhesus macaques for preclinical safety and dose estimation of TIGIT-targeted therapies."

Journal • Oncology • PVR • TIGIT

A Study of Immune Checkpoint Inhibitor Combinations With Axitinib in Participants With Untreated Locally Advanced Unresectable or Metastatic Renal Cell Carcinoma (clinicaltrials.gov) - P2 | N=199 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Oct 2025 ➔ Jul 2026 | Trial primary completion date: Oct 2025 ➔ Jul 2026

Checkpoint inhibition • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=314 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2026 ➔ Nov 2025

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Imbrave 152: A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC) (IMbrave152) (clinicaltrials.gov) - P3 | N=687 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Sep 2026 ➔ May 2025

Trial primary completion date • Hepatocellular Cancer • Oncology • Solid Tumor

SKYSCRAPER-07: A phase III, randomised study of atezolizumab (atezo) with or without tiragolumab (tira) in patients (pts) with unresectable esophageal squamous cell carcinoma (ESCC) that has not progressed following definitive concurrent chemoradiotherapy (dCRT) (DGHO 2025) - P3 | "SKYSCRAPER-07 did not meet its primary endpoint of PFS for tira + atezo vs pbo in pts with ESCC, and no OS benefit was observed vs pbo. However, results indicate a clinically meaningful improvement in PFS and OS with atezo + pbo vs pbo. No new safety signals were identified."

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

Nanomechanical Signatures Predict Response to Combination Immunotherapy and Low Dose Radiation Therapy in Advanced Solid Tumors (SITC 2025) - P1, P2 | "Clinically, our study includes patients recruited under two different studies at MDACC: the Salvage Radiation Therapy in Treating Patients with Metastatic Cancer That Has Progressed After Systemic Immunotherapy (NCT02710253, Phase II), and the Phase I/Ib Trial of TIraGolumab, AtEzolizumab, and RadScopal Radiation in Patients with Advanced Solid Malignancies (TIGER) study (NCT06760481, Phase I).Results Among our clinical results, initial exploratory evaluation of currently enrolled clinical cases reveals that ARTIDIS nanomechanical signature predicts the long term response to combination immunotherapy and RadScopal in advanced (stage IV) melanoma patients. All participants provided informed consent prior to their participation in the study. All animal experiments were conducted in strict accordance with institutional guidelines and regulations, and all protocols were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of The..."

IO biomarker • Metastases • Gastric Cancer • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor

Addition of Tiragolumab Fails to Improve Front-Line Outcomes in Advanced Hepatocellular Carcinoma (Oncology Learning Network) - "Richard Finn, MD...discusses results from the phase 3 IMbrave152/SKYSCRAPER-14 study evaluating tiragolumab in combination with atezolizumab and bevacizumab versus atezolizumab, bevacizumab, and placebo in patients with advanced hepatocellular carcinoma."

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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

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 (clinicaltrials.gov) - P2 | N=204 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2026 ➔ Mar 2026 | Trial primary completion date: Dec 2026 ➔ Mar 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • PD-L1

Combination TIGIT and PD-1 inhibition with VEGFR-2 based therapy induces potent response in patient derived immune competent xenograft model with gastroesophageal adenocarcinoma (AACR-NCI-EORTC 2025) - "Quadruplet therapy with tiragolumab, nivolumab, DC101, and paclitaxel resulted in significant tumor growth inhibition with 4/8 complete responses in this immune competent humanized mouse PDX model. These pre-clinical results support further development of this combination in clinical trials."

IO biomarker • Preclinical • Esophageal Adenocarcinoma • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CD34 • CD8 • FOXP3 • HAVCR2 • IFNG • SIRPA • TIGIT • TNFA

SKYSCRAPER-08: A Study of Atezolizumab Plus Tiragolumab in Combination With Paclitaxel and Cisplatin Compared With Paclitaxel and Cisplatin as First-Line Treatment in Participants With Unresectable Locally Advanced, Unresectable Recurrent, or Metastatic Esophageal Carcinoma (clinicaltrials.gov) - P3 | N=461 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | Trial completion date: Jan 2026 ➔ Aug 2025

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

Efficacy and safety of atezolizumab (Atezo) with or without tiragolumab (Tira) following neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (NEOTERIC): A multicenter, randomized, open-label, parallel-group phase II study (ESMO 2025) - P2 | "Eligible pts with resectable LARC (cT3N+M0 or cT4NanyM0) received long-course nCRT (45-50.4 Gy/25-28 fractions, and capecitabine 825mg/m 2 PO Bid or 5-FU 225mg/m 2 IV 5 days/week during RT), followed by Atezo 1200mg with or without Tira 600mg on Day 1 of each 21-day cycle for 3 cycles...No treatment-emergent deaths were observed. Conclusions Atezo with Tira following nCRT demonstrated a significantly higher pCR rate compared to the historical control and exhibited a manageable safety profile."

Clinical • Metastases • P2 data • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor

Tiragolumab/Atezolizumab/Bevacizumab Fails to Significantly Improve PFS in Advanced/Metastatic HCC (OncLive) - "'These data, now from a double-blind, placebo-controlled study of over 600 patients, confirm the activity of atezolizumab plus bevacizumab in the management of this population, as well as the safety, and moving forward, we will hopefully learn a lot from the study on how to best decide to move forward in advancing care for our patients with HCC,' study author and presenter, Richard S. Finn, MD, stated."

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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

SKYSCRAPER-07: A phase III, randomised study of atezolizumab (atezo) with or without tiragolumab (tira) in patients (pts) with unresectable esophageal squamous cell carcinoma (ESCC) that has not progressed following definitive concurrent chemoradiotherapy (dCRT) (ESMO 2025) - P3 | "No new safety signals were identified. Table: 2094O PFS OS A Tira + atezo (N=257) B Atezo + pbo (N=250) C Pbo + pbo (N=253) A Tira + atezo (N=257) B Atezo + pbo (N=250) C Pbo + pbo (N=253) Pts with event, n (%) 141 (54.9) 128 (51.2) 157 (62.1) 111 (43.2) 88 (35.2) 118 (46.6) Median, m (95% CI) 20.8 (13.9–28.8) 29.1 (19.0–36.3) 16.6 (11.2–19.4) 38.6 (28.8–NE) NR 36.4 (25.8–NE) Stratified HR* (95% CI) 0.82 (0.65–1.03) 0.74 (0.58–0.93) † – 0.91 (0.70–1.18) † 0.69 (0.52–0.91) † – P-value* 0.0947 0.0113 † – 0.4772 † 0.0085 † – 24 m rate, % (95% CI) 46.7 (40.3–53.0) 52.8 (46.4–59.2) 40.9 (34.6–47.1) 59.9 (53.6–66.1) 69.1 (63.2–75.0) 59.4 (53.1–65.7) *Vs placebo † Not formally tested as PFS (A vs C) not met, p-values are descriptive m, months; NE, not estimable; NR, not reached"

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

Tiragolumab Regimen Misses PFS End Point in Hepatocellular Carcinoma (Cancer Network) - "...According to a presentation on data from the phase 3 IMbrave152/SKYSCRAPER-14 study (NCT05904886) at the European Society for Medical Oncology Congress 2025....patients treated with placebo plus atezolizumab and bevacizumab (n = 338) had an investigator-assessed median PFS of 8.2 months (95% CI, 7.0-9.7) vs 8.3 months (95% CI, 7.1-9.8) in patients treated with tiragolumab plus atezolizumab plus bevacizumab (HR, 0.97; 95% CI, 0.8-1.2; stratified log-rank P =.7464). Overall survival (OS) data, at this time, remain immature, and are not anticipated to reach statistical significance, according to study authors."

P3 data • Hepatocellular Cancer

Tiragolumab Plus Tecentriq Doesn’t Improve NSCLC Outcomes (Cure Today) - "At a median follow-up of 30.7 months, the median IRF-PFS in the overall population was 14.2 months in patients receiving the combination versus 13.8 months in patients treated with Imfinzi. The 24-month PFS event-free rates were 39% and 38.5%, respectively. The median overall survival (OS) was 45.6 months versus 45.8 months, respectively."

P3 data • Non Small Cell Lung Cancer

Tiragolumab With Atezolizumab Plus Bevacizumab in Previously-Treated Advanced Non-squamous NSCLC (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: Georgetown University | Recruiting ➔ Active, not recruiting | N=42 ➔ 29

Enrollment change • Enrollment closed • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

SKYSCRAPER-07 at ESMO 2025: Tiragolumab Plus Atezolizumab After dCRT in Locally Advanced ESCC (OncoDaily) - "Progression-Free Survival (PFS): Arm A (tira + atezo): Median PFS 20.8 months (95% CI, 13.9–28.8); Arm B (atezo + placebo): Median PFS 29.1 months (95% CI, 19.0–36.3); Arm C (placebo): Median PFS 16.6 months (95% CI, 11.2–19.4)...Overall Survival (OS): Arm A: 38.6 months (95% CI, 28.8–NE); Arm B: Not reached (95% CI, NE); Arm C: 36.4 months (95% CI, 25.8–NE)...While the study did not meet its primary endpoint (PFS Arm A vs C), atezolizumab monotherapy demonstrated clinically meaningful improvement in both PFS and OS compared to placebo....Treatment-related adverse events (AEs) occurred in 74.8% of patients in the tiragolumab + atezolizumab arm, 65.2% in the atezolizumab arm, and 90% in the placebo arm."

P3 data • Esophageal Squamous Cell Carcinoma