tiragolumab (RG6058) / Roche - LARVOL DELTA

On the importance of the metrics used for assessing dual-tracer 18F-FDG – 68Ga-FAPI PET scans in triple negative breast cancer patients (SNMMI 2025) - P2 | " SKYLINE is an ongoing trial prospectively enrolling 160 pts with TNBC split in 2 cohorts: cohort A consists of pts with stage II-III TNBC treated with neoadjuvant therapy combining tiragolumab, atezolumab and chemotherapy before curative surgery, and cohort B includes pts with de novo or relapsed stage IV TNBC who receive nab-paclitaxel, atezolizumab and tiragolumab until disease progression or unacceptable toxicity. Twenty pts have been enrolled (cohort A: 14, cohort B: 6), with 16 scanned at the 2 time points, yielding 72 analyzed PET scans. In both cohorts at baseline, all primary lesions had elevated FDG and FAPI uptake (mean FDG SUVmax ± 1 sd =18.8±7.5, range [8.6-40.2] ; mean FAPI SUVmax=15.8±4.9, range [7.8-25.6]). In these primary lesions at baseline, FDG SUVmax was greater than FAPI SUVmax in 14 pts (cohort A: 10, cohort B: 4) and smaller in 6 pts (cohort A: 4, cohort B: 2). In cohort A, the mean rSUVmax in the..."

Clinical • IO biomarker • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • TIGIT

NeoACTIVATE: Vemurafenib, Cobimetinib, Atezolizumab, and Tiragolumab in Treating Patients With High-Risk Stage III Melanoma (clinicaltrials.gov) - P2 | N=59 | Active, not recruiting | Sponsor: Mayo Clinic | Trial completion date: Jun 2025 ➔ Nov 2027 | Trial primary completion date: Jun 2025 ➔ Nov 2027

Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

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

Phase 1/2 study of tiragolumab and atezolizumab in patients with relapsed or refractory SMARCB1- or SMARCA4-deficient tumors: PEPN2121. (ASCO 2025) - P1/2 | "Enrollment is open at all Pediatric Early Phase Clinical Trial Network sites. Data cutoff: Jan 10, 2025."

Clinical • IO biomarker • P1/2 data • Chordoma • Kidney Medullary Carcinoma • Oncology • Pediatrics • Renal Cell Carcinoma • Rhabdoid Tumor • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • NECTIN2 • PD-L1 • PVR • SMARCA4 • SMARCB1 • TIGIT

NeoTRACK - Dissection of IO Efficacy in NSCLC by Longitudinal tracKing (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Trial completion date: Feb 2030 ➔ Jun 2027 | Trial primary completion date: Nov 2029 ➔ Dec 2026 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

NOvel Immunotherapy strategies for advanced Triple negative breast Cancer: TONIC-3 trial (ESMO-BC 2025) - P2 | "This study evaluates the safety and efficacy of tiragolumab (anti-TIGIT) combined with atezolizumab (anti-PDL1) and/or ipilimumab (anti-CTLA4).Trial design: The TONIC-3 trial is a single-center, multi-cohort, non-comparative phase II trial enrolling patients with PD-L1 negative (CPS <10) or anti-PD(L)1 refractory advanced TNBC, with a maximum of three lines of prior palliative chemotherapy and/or antibody drug conjugate, disease-free interval longer than 1 year, a metastatic lesion accessible for a biopsy and LDH <500 U/I. For at least one third of the patients a metastatic lesion will be resected at baseline to generate ex vivo [Voabil et al, Nat Med 2021] response data. The TONIC-3 trial is currently open for enrollment at the Netherlands Cancer Institute."

Metastases • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • TIGIT

Unlocking the potential of TIGIT in enhancing therapeutic strategies for acute myeloid leukemia through combined azacitidine therapy. (PubMed, NPJ Precis Oncol) - "Additionally, our in vitro and in vivo studies showed that combining tiragolumab with azacitidine (AZA) synergistically enhanced anti-tumor efficacy, reducing tumor burden and extending survival in a murine AML model. Our findings underscore TIGIT's role in hematologic malignancies and its potential as a therapeutic target in AML. The combination of AZA with TIGIT inhibition offers a promising new approach for AML treatment, warranting further clinical evaluation."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • TIGIT

MORPHEUS-EC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G/GEJ) or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer) (clinicaltrials.gov) - P1/2 | N=410 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2025 ➔ Sep 2025 | Trial primary completion date: Jun 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2 • PD-L1 • TIGIT

AACR25: Roche details lung cancer survival miss for anti-TIGIT as "hopes…lower" (Firstwordpharma Press Release) - P3 | N=620 | SKYSCRAPER-01 (NCT04294810) | Sponsor: Hoffmann-La Roche | "At the American Association for Cancer Research (AACR) meeting on Monday, overall survival (OS) data from Roche's failed SKYSCRAPER-01 study of the anti-TIGIT therapy tiragolumab in PD-L1-high non–small-cell lung cancer (NSCLC) were presented. The results show that while median survival slightly improved from a previous interim analysis, the hazard ratio worsened....Data presented at AACR showed that median OS in the tiragolumab plus Tecentriq arm was 23.1 months, versus 16.9 months for Tecentriq alone, with a HR of 0.87....Roche is investigating the drug in liver cancer, with data from the Phase III SKYSCRAPER-14 study expected next year..."

P3 data • Hepatocellular Cancer • Liver Cancer • Non Small Cell Lung Cancer

HY07121, a new generation of immune oncology therapeutics overcoming tumor immune resistance (AACR 2025) - "In vivo, HY07121 exhibited dose-dependent tumor inhibition in both the human bladder cancer cell derived xenograft model and the immune-resistant human melanoma cell (A375) derived xenograft model, significantly outperforming the combination of Pembrolizumab and Tiragolumab. The in vitro and in vivo findings suggest that HY07121 is a novel, mechanism-driven therapeutic with the potential to enhance the efficacy of immunotherapy and address both primary and acquired resistance. The pharmacological and toxicological profiles strongly support the continued clinical development of HY07121."

Bladder Cancer • Genito-urinary Cancer • Melanoma • Oncology • Solid Tumor • CD8 • IFNG • IL15 • TIGIT

Unlocking the potential of TIGIT in enhancing therapeutic strategies for acute myeloid leukemia through combined azacitidine therapy (Nature, NPJ Precis Oncol) - "Our model outperformed traditional prognostic factors, highlighting TIGIT’s potential as a superior predictive biomarker. Additionally, our in vitro and in vivo studies showed that combining tiragolumab with azacitidine (AZA) synergistically enhanced anti-tumor efficacy, reducing tumor burden and extending survival in a murine AML model."

Preclinical • Acute Myelogenous Leukemia

Unlocking the potential of TIGIT in enhancing therapeutic strategies for acute myeloid leukemia through combined azacitidine therapy (Nature, NPJ Precis Oncol) - "Our model outperformed traditional prognostic factors, highlighting TIGIT’s potential as a superior predictive biomarker. Additionally, our in vitro and in vivo studies showed that combining tiragolumab with azacitidine (AZA) synergistically enhanced anti-tumor efficacy, reducing tumor burden and extending survival in a murine AML model."

Preclinical • Acute Myelogenous Leukemia

MORPHEUS-Liver: A Phase Ib/II, randomised study evaluating tiragolumab (tira) in combination with atezolizumab (atezo) and bevacizumab (bev) in patients (pts) with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC) (ESMO-GI 2025) - No abstract available

Clinical • Combination therapy • Metastases • P1/2 data • Hepatocellular Cancer • Oncology • 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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | N=150 ➔ 62

Enrollment change • Enrollment closed • Hepatocellular Cancer • Oncology • Solid Tumor

Tertiary Lymphoid Structures as Predictors of Immune Checkpoint Inhibitor Efficacy in NSCLC and the Development of an Ex Vivo Model for Precision Medicine (AACR 2025) - P=N/A | "On the other hand, the ex vivo model demonstrated robust IgG production in Tfh-B cell co-cultures, modulated positively by ICIs (Nivolumab, Atezolizumab, Tiragolumab, Ipilimumab) and negatively by anti-CD40 and kynurenine. This study highlights the critical role of TLS maturity in predicting response to ICIs and improving survival outcomes in NSCLC. This study highlights the critical role of TLS maturity in predicting response to ICIs and improving survival outcomes in NSCLC. The ex vivo Tfh-B cell model provides a novel platform to evaluate therapies targeting TLS function. Combining TLS stratification via histology with Tfh-B cell synapse-enhancing agents represents a promising approach in precision medicine."

Checkpoint inhibition • IO biomarker • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD27 • CXCR5 • FCER2 • PD-L1 • TIGIT

Assessing strategies to activate DNAM1 signaling and inhibit the TIGIT/PVRIG axis using mathematical modeling (AACR 2025) - "The combination of PVR and PVRIG blockade resulted in the strongest increase in engaged DNAM1 (approximately 2-fold), in addition to disrupting TIGIT, CD96, and PVRIG engagements.The inability to increase DNAM1 engagement during TIGIT inhibition may be one of the reasons for the lack of efficacy observed in the phase 3 trial of tiragolumab (anti-TIGIT mAb) used in combination with atezolizumab. Targeting PVR alone or in combination with PVRIG appears to be a better strategy than targeting TIGIT or TIGIT in combination with PVRIG."

IO biomarker • Oncology • CD226 • CD8 • CD96 • NECTIN2 • PVR • 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

Phase I/Ib Trial of TIraGolumab, AtEzolizumab, and RadScopal Radiation in Patients With Advanced Solid Malignancies (TIGER) (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

Tecentriq + Tiragolumab: Regulatory submission in Japan for esophageal cancer and stage III NSCLC in 2025 (Chugai) - Q1 FY2025 Results: Regulatory submission in Japan in combination with Avastin for 1L HCC in 2026

Japan filing • Esophageal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Tecentriq + Tiragolumab: Regulatory submissions in US/EU for stage III unresectable 1L NSCLC in 2025 (Roche) - Q1 2025 Results: Regulatory submissions in US/EU in combination with avastin for 1L HCC in 2026

EMA filing • FDA filing • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology

A Phase 2 Clinical Trial Evaluating the Efficacy and Safety of Dual Immune Checkpoint Inhibition With Anti-PD-L1 (Atezolizumab) and Anti-TIGIT (Tiragolumab) in Cancer of Unknown Primary (clinicaltrials.gov) - P2 | N=35 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Oncology

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=341 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

CITYSCAPE: A Study of Tiragolumab in Combination With Atezolizumab in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=135 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Mar 2025 ➔ Aug 2025

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

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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Sep 2024 ➔ Dec 2025

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

A non-comparative, randomized, phase II trial of atezolizumab or atezolizumab plus tiragolumab for programmed death-ligand 1-positive recurrent cervical cancer (SKYSCRAPER-04). (PubMed, Int J Gynecol Cancer) - P2 | "The objective response rate with the tiragolumab-plus-atezolizumab combination was numerically higher than the historical reference but did not reach statistical significance."

Clinical • Journal • P2 data • Cervical Cancer • Oncology • Solid Tumor • PD-L1 • TIGIT