tobemstomig (RG6139) / Roche - LARVOL DELTA

A Study of Multiple Doses of RO7247669 in Participants With Previously Untreated Unresectable or Metastatic Melanoma (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Hoffmann-La Roche | Phase classification: P1/2 ➔ P2

Phase classification • Melanoma • Oncology • Solid Tumor • BRAF • 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=506 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2025 ➔ Aug 2026 | Trial primary completion date: Dec 2025 ➔ Aug 2026

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

A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma) (clinicaltrials.gov) - P1/2 | N=110 | Completed | Sponsor: Hoffmann-La Roche | Recruiting ➔ Completed | N=336 ➔ 110 | Trial completion date: Jul 2025 ➔ Mar 2024 | Trial primary completion date: Jan 2025 ➔ Sep 2023

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • CD4

A Study of Tobemstomig Plus Platinum-Based Chemotherapy vs Pembrolizumab Plus Platinum-Based Chemotherapy in Participants With Previously Untreated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting

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

Tobemstomig, a novel bispecific checkpoint inhibitory antibody to preferentially block PD-1 and LAG-3 on CD8 TILs over Tregs (AACR 2024) - "LAG-3 is constitutively expressed by regulatory T cells (on Tregs) and it has been reported that its blockade increases Treg suppressive function which could potentially off-sets the benefit of blocking LAG-3 on tumor-reactive CD8 T cells.We therefore developed a 1+1 PD1-LAG3 bispecific antibody, Tobemstomig, with a unique PD-1 binder recognizing a glycoepitope and more than 20 fold higher affinity than the LAG-3 binder which recognizes a novel and differentiated binding epitope (E3). This difference in affinities allows for an avidity driven selectivity gain to PD-1 and LAG-3 double positive T cells over and the following advantages over monospecific and other bispecific aPD-1/-L1 and aLAG-3 antibodies:1.improved targeting to tumor-reactive T cells rather than Tregs due to the selectivity gain and different expression patterns of PD-1 and LAG-3 on these two T cell types, 2.reduced internalization, 3.resistance to drug-shaving by macrophages due to Fc -silencing via..."

Checkpoint inhibition • IO biomarker • Oncology • Solid Tumor • CD8 • LAG3

A Study of Tobemstomig Plus Platinum-Based Chemotherapy vs Pembrolizumab Plus Platinum-Based Chemotherapy in Participants With Previously Untreated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=180 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Feb 2027 ➔ Sep 2028 | Trial primary completion date: May 2025 ➔ Sep 2025

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

A Study of Multiple Doses of RO7247669 in Participants With Previously Untreated Unresectable or Metastatic Melanoma (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: Hoffmann-La Roche | Phase classification: P2 ➔ P1/2

Metastases • Phase classification • Melanoma • Oncology • Solid Tumor • BRAF • PD-L1

A global, multicentre, open-label, randomised phase II trial of tobemstomig (tobe) with or without tiragolumab (tira) vs atezolizumab (atezo) in patients (pts) with untreated metastatic urothelial cancer (mUC) ineligible for platinum-based chemotherapy (chemo) (ESMO 2023) - P2 | "This study will evaluate the effect of tobe and tobe + tira on investigator-assessed confirmed ORR (primary endpoint) relative to atezo. Secondary endpoints include PFS, OS, DOR, DCR and safety."

Clinical • IO biomarker • Metastases • P2 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • LAG3 • TIGIT

ESMO 2023: Phase II Trial Compares Tobemstomig Alone or with Tiragolumab vs. Atezolizumab in Untreated Metastatic Urothelial Cancer (Urotoday) - "The 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20th and 24th, 2023 hosted a urothelial and other cancers abstract poster session for trials in progress. Dr. Shilpa Gupta presented the study framework for a global, multicentre, open-label, randomised phase II trial of tobemstomig with or without tiragolumab versus atezolizumab in patients with untreated metastatic urothelial cancer ineligible for platinum-based chemotherapy....In this trial, the efficacy and safety of atezolizumab (Arm A, control) versus tobemstomig (Arm B) or tobemstomig + tiragolumab (Arm C) will be evaluated as 1st line therapy in platinum-ineligible patients with metastatic urothelial carcinoma....Patients will be recruited from 83 sites across 15 countries and randomized 1:1:1 to receive: Atezolizumab 1,200 mg IV; Tobemstomig 600 mg IV every 3 weeks; Tobemstomig 600 mg IV + tiragolumab 600 mg IV every 3 weeks."

Trial status • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor

A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma) (clinicaltrials.gov) - P1/2 | N=336 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Oct 2024 ➔ Jan 2025

Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • CD4

A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma) (clinicaltrials.gov) - P1/2 | N=336 | Recruiting | Sponsor: Hoffmann-La Roche | N=191 ➔ 336 | Trial completion date: Mar 2024 ➔ Jul 2025 | Trial primary completion date: Nov 2023 ➔ Oct 2024

Enrollment change • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • CD4

A Study of Lomvastomig (RO7121661) and Tobemstomig (RO7247669) Compared With Nivolumab in Participants With Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus (clinicaltrials.gov) - P2 | N=210 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Metastases • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology • Squamous Cell Carcinoma • CD4 • CD8 • HAVCR2 • LAG3 • PD-1

A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma (clinicaltrials.gov) - P1/2 | N=150 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P1/2 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor

A Study of RO7247669 + Nab-Paclitaxel Compared With Pembrolizumab + Nab-Paclitaxel in Participants With Previously Untreated, PD-L1-Positive, Locally-Advanced Unresectable or Metastatic Triple-Negative Breast Cancer (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • ER • HER-2 • PD-L1

A Study of RO7247669 + Nab-Paclitaxel Compared With Pembrolizumab + Nab-Paclitaxel in Participants With Previously Untreated, PD-L1-Positive, Locally-Advanced Unresectable or Metastatic Triple-Negative Breast Cancer (clinicaltrials.gov) - P2 | N=160 | Not yet recruiting | Sponsor: Hoffmann-La Roche

Metastases • New P2 trial • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • ER • HER-2 • PD-L1

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=210 | Recruiting | Sponsor: Hoffmann-La Roche

Checkpoint inhibition • Metastases • New P2 trial • Genito-urinary Cancer • Immune Modulation • Oncology • Renal Cell Carcinoma • Solid Tumor

Dose Escalation Study of a PD1-LAG3 Bispecific Antibody in Patients With Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=320 | Recruiting | Sponsor: Hoffmann-La Roche | Phase classification: P1 ➔ P1/2

Metastases • Phase classification • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

A Study of RO7247669 Plus Platinum-Based Chemotherapy vs Pembrolizumab Plus Platinum-Based Chemotherapy in Participants With Previously Untreated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Hoffmann-La Roche

IO biomarker • Metastases • New P2 trial • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

A Study of RO7247669 Alone or in Combination with Tiragolumab Versus Atezolizumab in Patients with Previously Untreated Locally Advanced or Metastatic Urothelial Bladder Cancer who are Ineligible for Platinum-Containing Chemotherapy (clinicaltrialsregister.eu) - P2 | N=240 | Ongoing | Sponsor: F. Hoffmann-La Roche Ltd

Combination therapy • Metastases • New P2 trial • Back Pain • Bladder Cancer • Genito-urinary Cancer • Musculoskeletal Pain • Oncology • Pain • 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=320 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jul 2025 ➔ Dec 2025 | Trial primary completion date: Jul 2025 ➔ Dec 2025

Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • PD-L1

A Study of RO7247669 Alone or in Combination With Tiragolumab vs Atezolizumab in Participants With Untreated Locally Advanced or Metastatic Urothelial Cancer (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • PD-L1

Ministry of Food and Drug Safety, Chong Kun Dang approved 8 clinical trials including new drugs for dyslipidemia [Google translation] (Health Korea News) - "Roche Korea has been approved for a phase 2 study of 'RO7247669', a treatment for urothelial cancer. 29 domestic patients with locally advanced or metastatic urothelial cancer who have not been previously treated and are unsuitable for platinum-containing chemotherapy will study 'RO7247669' monotherapy or combination therapy with tiragolumab versus atezolizumab therapy. The test will be conducted at six institutions including Gil Hospital."

New P2 trial • Genito-urinary Cancer • Oncology • Urothelial Cancer

A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma) (clinicaltrials.gov) - P1/2 | N=191 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Oct 2023 ➔ Mar 2024 | Trial primary completion date: Apr 2023 ➔ Nov 2023

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