tiragolumab (RG6058) / Roche - LARVOL DELTA

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-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 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

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: Mar 2026 ➔ Dec 2026 | Trial primary completion date: Mar 2026 ➔ Dec 2026

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

A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC) (clinicaltrials.gov) - P1 | N=542 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2028 ➔ Aug 2030 | Trial primary completion date: Aug 2027 ➔ Aug 2030

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

MORPHEUS mUC: Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC) (clinicaltrials.gov) - P1/2 | N=272 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

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

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 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2026 ➔ Dec 2027 | Trial primary completion date: Dec 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Liver Cancer • Oncology • Solid Tumor • PD-L1

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 TTrefractory, 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

SKYSCRAPER-01: A Study of Tiragolumab in Combination With Atezolizumab Compared With Placebo in Combination With Atezolizumab in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1-Selected Non-Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=620 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

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

Preoperative immunotherapy with atezolizumab and tiragolumab in patients with colorectal liver metastases-the PURPLE trial. (PubMed, ESMO Gastrointest Oncol) - "Secondary endpoints include feasibility, safety, post-operative complications, and metabolic response by positron emission tomography. Exploratory studies characterize immune cell infiltration, tumor mutational burden, and circulating tumor DNA dynamics."

IO biomarker • Journal • Tumor mutational burden • Colorectal Cancer • Oncology • Solid Tumor • TIGIT • TMB

SKYSCRAPER-15: A Study of Tiragolumab Plus Atezolizumab Compared With Placebo Plus Atezolizumab in Participants With Completely Resected Non-small Cell Lung Cancer Who Have Received Adjuvant Platinum-based Chemotherapy (clinicaltrials.gov) - P3 | N=56 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

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

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

First-line tiragolumab plus atezolizumab and chemotherapy in patients with previously untreated, locally advanced unresectable or metastatic oesophageal cancer (MORPHEUS-EC): a randomised, open-label, phase 1b/2 trial. (PubMed, Lancet Oncol) - P1/2, P3 | "These results support the additional benefit of tiragolumab combined with atezolizumab and chemotherapy for patients with treatment-naive, locally advanced unresectable or metastatic oesophageal cancer. Further validation of tiragolumab plus atezolizumab and chemotherapy has been performed in the phase 3 SKYSCRAPER-08 trial (NCT04540211)."

Clinical • Journal • P1/2 data • Esophageal Cancer • Oncology • Solid Tumor • TIGIT

SKYLINE: Tiragolumab, Atezolizumab and Chemotherapy in Triple Negative Breast Cancer (clinicaltrials.gov) - P2 | N=81 | Active, not recruiting | Sponsor: Institut Curie | Recruiting ➔ Active, not recruiting | N=130 ➔ 81

Enrollment change • Enrollment closed • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PD-L1 • PGR

SKYSCRAPER-06: Efficacy and safety of tiragolumab plus atezolizumab plus chemotherapy (tira + atezo + chemo) vs pembrolizumab plus chemotherapy (pembro + chemo) in patients (pts) with advanced non-squamous non-small cell lung cancer (NSq NSCLC) (ESMO-IO 2024) - P2/3 | "Pts were randomised 1:1 to receive tira 600 mg IV + atezo 1200 mg IV + carboplatin/cisplatin + pemetrexed IV or placebo + pembro 200 mg IV + carboplatin/cisplatin + pemetrexed IV, every 3 weeks for 4 cycles, followed by maintenance therapy with tira + atezo + pemetrexed or placebo + pembro + pemetrexed until disease progression, loss of clinical benefit, unacceptable toxicity or consent withdrawal. Median PFS was 8.3 vs 9.9 months and median OS was 18.9 vs 23.1 months in the tira + atezo + chemo and the pembro + chemo arms, respectively (Table). Tira + atezo + chemo demonstrated an acceptable safety profile with no new safety signals; safety was generally similar between arms Conclusions In the SKYSCRAPER-06 study, tira + atezo + chemo failed to improve PFS and OS vs pembro + chemo in pts with advanced NSq NSCLC."

Clinical • IO biomarker • Late-breaking abstract • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

R&D activities: Oncology (Chugai Press Release) - "We decided to discontinue the development of an anti-TIGIT human monoclonal antibody RG6058 for nonsmall cell lung cancer (1st Line), non-small cell lung cancer (stage III ), esophageal cancer, all in combination with Tecentriq, and hepatocellular carcinoma (1st Line) in combination with Tecentriq and Avastin, considering the results of global Phase III studies SKYSCRAPER-01, SKYSCRAPER-03, SKYSCRAPER07, and SKYSCRAPER-14, respectively. We decided to discontinue the development of an anti-HER2/CD3 bispecific antibody RG6194 for solid tumors in consideration of business strategy."

Discontinued • Esophageal Cancer • Hepatocellular Cancer • Non Small Cell Lung Cancer • Solid Tumor

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

Tiragolumab and Atezolizumab in Patients With Non-squamous Non-small Cell Lung Cancer (NSCLC) and Untreated Brain Metastases (clinicaltrials.gov) - P2 | N=3 | Terminated | Sponsor: Liza Villaruz, MD | Trial completion date: Aug 2026 ➔ Nov 2025 | Active, not recruiting ➔ Terminated; Decision by agent provider

Trial completion date • Trial termination • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • PD-L1

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

Atezolizumab plus tiragolumab in combination with chemoradiotherapy in localized squamous cell carcinoma of the anal canal: TIRANUS (GEMCAD-2103) trial. (ASCO-GI 2026) - P2 | "The addition of A and T to CRT was feasible and generally well tolerated. Further follow-up is warranted to confirm efficacy and assess long-term benefit in reducing the need for surgical rescue."

Combination therapy • IO biomarker • Anal Carcinoma • Gastrointestinal Cancer • Oncology • TIGIT

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

Tiragolumab With Atezolizumab Plus Bevacizumab in Previously-Treated Advanced Non-squamous NSCLC (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: Georgetown University | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

Phase I-II trial of perioperative chemotherapy plus atezolizumab and tiragolumab in localized esophageal and gastroesophageal junction adenocarcinoma. (ASCO-GI 2026) - P2 | "Results indicate that atezolizumab and tiragolumab in combination with oxaliplatin and 5-fluorouracil has an acceptable safety profile providing high rate of tumor regression. This trial supports further research checkpoint inhibition in patients with localized esophageal and GEJ adenocarcinomas in the perioperative setting. Clinical trial information: NCT03784326."

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