tobemstomig (RG6139) / 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

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

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

Neoadjuvant PD-1 and LAG-3-targeting bispecific antibody and other immune checkpoint inhibitor combinations in resectable melanoma: the randomized phase 1b/2 Morpheus-Melanoma trial. (PubMed, Nat Med) - P1/2 | "The NADINA trial evaluating neoadjuvant nivolumab plus ipilimumab and the SWOG-1801 trial evaluating neoadjuvant pembrolizumab have demonstrated superior clinical outcomes with neoadjuvant versus adjuvant checkpoint inhibition...Tobemstomig plus tiragolumab and atezolizumab plus tiragolumab showed a lower pRR versus nivolumab plus ipilimumab (60.0% (12/20) and 45.0% (9/20) versus 77.3% (17/22), respectively)...In conclusion, in the Morpheus-Melanoma study, tobemstomig demonstrated a similar pathological response and improved safety profile versus nivolumab plus ipilimumab in patients with resectable stage III melanoma. ClinicalTrials.gov identifier: NCT05116202 ."

Checkpoint inhibition • IO biomarker • Journal • P1/2 data • Tumor mutational burden • Melanoma • Oncology • Solid Tumor • CD8 • IFNG • LAG3 • TIGIT • TMB

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 2026 ➔ Oct 2025 | Trial primary completion date: Oct 2026 ➔ Oct 2025

Checkpoint inhibition • Trial completion date • Trial primary completion date • Genito-urinary Cancer • 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=170 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

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

A phase II trial of tobemstomig (tobe) + platinum-based chemotherapy (chemo) vs pembrolizumab (pembro) + chemo in patients (pts) with untreated locally advanced or metastatic non-small cell lung cancer (NSCLC) (ELCC 2025) - P2 | "BO44178 (NCT05775289) is a randomised, double-blind, phase II study evaluating tobe + chemo vs pembro + chemo in pts with NSCLC who are ineligible for surgery or definitive chemoradiotherapy. Eligible pts with previously untreated, locally advanced unresectable or metastatic NSCLC were randomised 1:1 to receive either induction tobe + chemo (carboplatin + paclitaxel/pemetrexed) or pembro + chemo for four 21-day cycles, followed by maintenance tobe or pembro with/without pemetrexed every 3 weeks until disease progression, toxicity or loss of clinical benefit. At this interim analysis, no ORR or PFS benefit was observed in pts with untreated locally advanced or metastatic NSCLC receiving tobe + chemo over pembro + chemo. OS data remain immature."

Clinical • IO biomarker • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • LAG3 • PD-L1

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=206 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | Trial completion date: Jun 2025 ➔ Jan 2025 | Trial primary completion date: Jun 2025 ➔ Jan 2025

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

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 primary completion date: May 2025 ➔ Oct 2026

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

A Study of Tobemstomig + 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=83 | Active, not recruiting | Sponsor: Hoffmann-La Roche | N=160 ➔ 83

Enrollment change • 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 Multiple Doses of RO7247669 in Participants With Previously Untreated Unresectable or Metastatic Melanoma (clinicaltrials.gov) - P1/2 | N=93 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Phase classification: P2 ➔ P1/2

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

Dose Escalation Study of a PD1-LAG3 Bispecific Antibody in Patients With Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=170 | Active, not recruiting | Sponsor: Hoffmann-La Roche | N=320 ➔ 170

Enrollment change • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

A Study of Tobemstomig + 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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | Trial completion date: Feb 2026 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Enrollment closed • Metastases • Trial completion date • Trial primary completion date • 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 Multiple Doses of RO7247669 in Participants With Previously Untreated Unresectable or Metastatic Melanoma (clinicaltrials.gov) - P2 | N=93 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | Trial primary completion date: Oct 2025 ➔ May 2024

Enrollment closed • Trial primary completion date • 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=518 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Aug 2026 ➔ Dec 2026 | Trial primary completion date: Aug 2026 ➔ Dec 2026

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

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 | Trial completion date: Mar 2028 ➔ Jun 2026 | Trial primary completion date: Mar 2026 ➔ Jun 2024

Metastases • Trial completion date • Trial primary completion date • 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 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=210 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • 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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2026 ➔ Oct 2026 | Trial primary completion date: Sep 2024 ➔ May 2025

Checkpoint inhibition • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Genito-urinary Cancer • 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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • 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 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