tiragolumab (RG6058) / Roche - LARVOL DELTA

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=290 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2022 ➔ Jun 2024 | Trial primary completion date: Nov 2022 ➔ Jun 2024

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

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=290 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

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=250 | Recruiting | Sponsor: Hoffmann-La Roche | N=410 ➔ 250

Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • PD-L1

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=290 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2021 ➔ Nov 2022 | Trial primary completion date: Nov 2021 ➔ Nov 2022

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

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=340 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

INDIGO: Targeting PD-L1 and TIGIT in Tumors With Tertiary Lymphoid Structures (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Gustave Roussy, Cancer Campus, Grand Paris | N=115 ➔ 0 | Trial completion date: Jan 2030 ➔ Sep 2025 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Jan 2028 ➔ Sep 2025

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

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

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 | N=675 ➔ 314

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

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 • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

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 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

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

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=410 | Recruiting | Sponsor: Hoffmann-La Roche | N=292 ➔ 410

Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • PD-L1

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=307 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

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

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=435 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Feb 2024 ➔ Nov 2023

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

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

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=205 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2020 ➔ Feb 2022 | Trial primary completion date: Nov 2019 ➔ Feb 2022

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

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=380 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Apr 2022 ➔ Nov 2023

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

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=675 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Jun 2026 ➔ Sep 2025 | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2027 ➔ Nov 2026

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

SKYSCRAPER-05: A Study Evaluating the Safety and Efficacy of Neoadjuvant and Adjuvant Tiragolumab Plus Atezolizumab, With or Without Platinum-Based Chemotherapy, in Participants With Previously Untreated Locally Advanced Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=50 | Terminated | Sponsor: Hoffmann-La Roche | Completed ➔ Terminated; Study was terminated as data became available from Phase 3 trials of perioperative regimens combining chemotherapy with immunotherapy showing improved efficacy outcomes versus chemotherapy alone.

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

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=260 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Feb 2022 ➔ Nov 2021 | Trial primary completion date: Feb 2022 ➔ Nov 2021

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • 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 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

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=340 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Oct 2026 ➔ Jan 2025 | Trial primary completion date: Oct 2025 ➔ Jan 2025

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

Integrated single-cell analysis identifies biomarkers associated with clinical benefit in patients with PD-L1 positive, advanced NSCLC treated with SBRT followed by atezolizumab plus tiragolumab (AACR 2026) - "In PD-L1 positive oligometastatic NSCLC, atezolizumab plus tiragolumab after completion of SBRT improves PFS with manageable safety profile. Combination therapy boosts cytotoxic/helper T-cell programs in CB, whereas persistent ICAM/Galectin-CTLA4-driven Tregs underlie resistance to treatment."

Biomarker • Clinical • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • CXCL13 • PD-L1 • TIGIT

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=470 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Aug 2025 ➔ Nov 2026 | Trial primary completion date: Apr 2024 ➔ Aug 2025

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

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=675 | Recruiting | Sponsor: Hoffmann-La Roche | N=470 ➔ 675 | Trial completion date: Nov 2026 ➔ Sep 2027 | Trial primary completion date: Aug 2025 ➔ Jun 2026

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

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