ezabenlimab (BI 754091) / Boehringer Ingelheim - LARVOL DELTA

An open-label, phase Ib trial of the SIRPα inhibitor BI 765063 in combination with the PD-1 inhibitor ezabenlimab and cetuximab in patients (pts) with head and neck squamous cell carcinoma. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT05249426 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Combination therapy • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • SIRPA

An open-label, phase I trial of the SIRPα monoclonal antibody, BI 770371, alone and in combination with the PD-1 inhibitor ezabenlimab in patients with advanced solid tumors. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT05327946 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Combination therapy • Metastases • P1 data • Oncology • Solid Tumor • SIRPA

A Study to Test How BI 765063 and BI 770371 Are Taken up in Tumours of People With Different Types of Advanced Cancer Who Are Also Taking Ezabenlimab (clinicaltrials.gov) - P1 | N=13 | Recruiting | Sponsor: Boehringer Ingelheim | Trial primary completion date: Jun 2025 ➔ Oct 2025

Trial primary completion date • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • SIRPA

A Study to Test How BI 765063 and BI 770371 Are Taken up in Tumours of People With Different Types of Advanced Cancer Who Are Also Taking Ezabenlimab (clinicaltrials.gov) - P1 | N=13 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Oct 2025 ➔ Dec 2026

Trial completion date • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • SIRPA

A Study in People With Advanced Cancer to Test How Well Different Doses of BI 770371 Alone or in Combination With Ezabenlimab Are Tolerated (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Jun 2026 ➔ Sep 2025

Trial completion date • Oncology • Solid Tumor

A Study to Test Whether Different Combinations of BI 765063, Ezabenlimab, Chemotherapy, Cetuximab, and BI 836880 Help People With Head and Neck Cancer or Liver Cancer (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Apr 2026 ➔ Jul 2026

Trial completion date • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • SIRPA

A Study to Test How Well Different Doses of Obrixtamig (BI 764532) in Combination With Ezabenlimab Are Tolerated by People With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for DLL3 (clinicaltrials.gov) - P1/2 | N=45 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

A Study to Test BI 765179 Alone and in Combination With Ezabenlimab in Patients With Advanced Cancer (Solid Tumors) and BI 765179 in Combination With Pembrolizumab in Patients With Advanced Head and Neck Cancer (clinicaltrials.gov) - P1 | N=160 | Recruiting | Sponsor: Boehringer Ingelheim | Trial primary completion date: Aug 2027 ➔ Jan 2027

Trial primary completion date • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

A Study to Test Whether Different Combinations of BI 765063, Ezabenlimab, Chemotherapy, Cetuximab, and BI 836880 Help People With Head and Neck Cancer or Liver Cancer (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Aug 2025 ➔ Apr 2026

Trial completion date • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • SIRPA

A Study to Test How Different Doses of BI 1703880 in Combination With Ezabenlimab Are Tolerated in People With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1 | N=66 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: May 2027 ➔ Sep 2028 | Trial primary completion date: Mar 2027 ➔ Sep 2028

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

A Study in People With Advanced Cancer to Test How Well Different Doses of BI 770371 Alone or in Combination With Ezabenlimab Are Tolerated (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Mar 2025 ➔ Jun 2026

Trial completion date • Oncology • Solid Tumor

A Study to Test How Different Doses of BI 1703880 in Combination With Ezabenlimab Are Tolerated in People With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1 | N=66 | Recruiting | Sponsor: Boehringer Ingelheim | Trial primary completion date: Jan 2025 ➔ Mar 2027

Trial primary completion date • Oncology • Solid Tumor

A Study to Test How Well Different Doses of Obrixtamig (BI 764532) in Combination With Ezabenlimab Are Tolerated by People With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for DLL3 (clinicaltrials.gov) - P1/2 | N=43 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Jun 2025 ➔ Sep 2025 | Trial primary completion date: Jun 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

KISIMA-01: Phase 1b Study to Evaluate ATP128, VSV-GP128 and BI 754091, in Patients With Stage IV Colorectal Cancer (clinicaltrials.gov) - P1 | N=96 | Active, not recruiting | Sponsor: Amal Therapeutics | Trial completion date: Dec 2024 ➔ Aug 2025 | Trial primary completion date: Jul 2024 ➔ May 2025

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

Platform Trial Evaluating Safety and Efficacy of BI 754091 Anti- PD-1 Based Combination Therapies in PD-(L)1 naïve and PD- (L)1 Pretreated Patient Populations With Advanced/Metastatic Solid Tumours (clinicaltrials.gov) - P2 | N=212 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Dec 2024 | Trial primary completion date: May 2025 ➔ Dec 2024

Trial completion • Trial completion date • Trial primary completion date • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Lung Cancer • Oncology • Solid Tumor

Open-label, phase Ia study of STING agonist BI 1703880 plus ezabenlimab for patients with advanced solid tumors. (PubMed, Future Oncol) - P1 | "The primary endpoint is dose-limiting toxicities during the maximum tolerated dose evaluation period. Results will inform the future development of BI 1703880 for treatment of metastatic or recurrent malignancies.Clinical Trial number: NCT05471856."

Journal • P1 data • Oncology • Solid Tumor • STING

A Study Evaluating Different Doses of BI 765049 When Given Alone and When Given With Ezabenlimab to Patients With Advanced Solid Tumors Expressing the Protein B7-H6 on the Cell Surface (clinicaltrials.gov) - P1 | N=67 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed | Trial completion date: Dec 2028 ➔ Nov 2024 | Trial primary completion date: Dec 2025 ➔ Nov 2024

Trial completion • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • NCR3LG1

INTERACT-ION: Anti-PD-1 and mDCF Followed by Chemoradiotherapy in Patients With Stage III Squamous Cell Anal Carcinoma. (clinicaltrials.gov) - P2 | N=55 | Active, not recruiting | Sponsor: Centre Hospitalier Universitaire de Besancon | Trial primary completion date: Jul 2024 ➔ Nov 2024

Trial primary completion date • Anal Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma

Modulation of the intratumoral immune microenvironment by local therapy with natural killer cells engineered with a HER2-targeted chimeric antigen receptor in combination with systemic anti-PD-1 checkpoint inhibition in patients with recurrent glioblastoma (SNO 2024) - "In the multicenter CAR2BRAIN phase I first-in-human clinical trial, we investigated the modulation of the tumor microenvironment by repetitive local injection of clonal chimeric antigen receptor (CAR)-NK cells (NK-92/5.28.z) targeting HER2 alone and in combination with systemic anti-PD-1 checkpoint inhibitor therapy in patients with recurrent HER2-positive GB. Local immunotherapy with HER2-targeted CAR-NK cells is feasible and safe both as monotherapy and in combination with the systemic checkpoint inhibitor ezabenlimab and induces local immune reactions in CSF and tumor tissue. Given the signal for possible clinical benefit provided by the increase in PFS in the patients of the biopsy-treat-resect-treat cohort, further trials are warranted."

Checkpoint inhibition • Clinical • Combination therapy • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD4 • CD8 • FOXP3 • HER-2

A Study Evaluating Different Doses of BI 765049 When Given Alone and When Given With Ezabenlimab to Patients With Advanced Solid Tumors Expressing the Protein B7-H6 on the Cell Surface (clinicaltrials.gov) - P1 | N=67 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting | N=248 ➔ 67

Enrollment change • Enrollment closed • Metastases • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • NCR3LG1

A Study to Test Different Doses of BI 836880 Combined With Ezabenlimab in Patients With Advanced Non-small Cell Lung Cancer Followed by Other Types of Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=252 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

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

First results for intravenous (IV) VSV-GP (BI 1831169) in patients (pts) with advanced solid tumors from the 1456-0001 study (ESMO 2024) - P1 | "Here we present the first results for the IV administration of the VSV-GP in pts with advanced solid tumors. The 1456-0001 study (NCT05155332) is a Phase I, open-label, dose-escalation study evaluating intratumoral (IT), IV, or IT+IV VSV-GP as monotherapy (Part 1) or in combination with the anti-PD-1 antibody ezabenlimab (Part 2). The study is ongoing to determine the MTD of IV VSV-GP monotherapy."

Clinical • Metastases • Oncology • Solid Tumor

Updated results from the phase I 1456-0001 study for intratumoral (IT) VSV-GP (BI 1831169) in patients with advanced solid tumors (ESMO 2024) - P1 | "Here we report updated results for IT VSV-GP monotherapy. In this Phase I, open-label, dose-escalation study, VSV-GP is administered IT, intravenously (IV), or IT+IV as monotherapy (Part 1) or with the anti-PD-1 antibody ezabenlimab (Part 2). The study is ongoing to evaluate safety and determine the MTD of IT VSV-GP monotherapy."

Clinical • Metastases • P1 data • Oncology • Solid Tumor

Systemic STING agonist BI 1703880 plus ezabenlimab in patients (pts) with advanced solid tumors: Initial results from a phase Ia study (ESMO 2024) - P1 | "The study is ongoing to evaluate DLTs and determine the recommended expansion dose. Clinical benefit has been observed with manageable safety."

Clinical • Metastases • P1 data • Oncology • Solid Tumor • IFNB1 • IFNG

Repetitive intracranial injection of natural killer cells engineered with a HER2-targeted chimeric antigen receptor alone and in combination with systemic anti-PD-1 checkpoint inhibition in patients with recurrent glioblastoma (EANO 2024) - "In the multicenter CAR2BRAIN phase I first-in-human clinical trial, we investigated repetitive local adoptive transfer of clonal chimeric antigen receptor (CAR)-NK cells (NK-92/5.28.z) targeting HER2 alone and in combination with the anti-PD-1 checkpoint inhibitor ezabenlimab in patients with recurrent HER2-positive GB. Immunotherapy with repetitive intracranial injection of HER2-targeted CAR-NK cells is feasible and safe both as monotherapy and in combination with the systemic checkpoint inhibitor ezabenlimab, and favorably modulates the intratumoral immune microenvironment. Given the highly promising results obtained so far, further trials are warranted to confirm the potential clinical benefit of this strategy."

Checkpoint inhibition • Clinical • Combination therapy • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD4 • CD8 • FOXP3 • HER-2