BI 836880 / 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 | "This Phase Ib study (NCT05249426) is investigating the efficacy and safety of BI 765063 in combination with ezabenlimab + cetuximab (Cohort A) or ezabenlimab + chemotherapy (Cohort B) in pts with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), or in combination with ezabenlimab ± BI 836880 (anti-VEGF/Ang2) in pts with hepatocellular carcinoma. These preliminary data indicate that BI 765063 in combination with ezabenlimab and cetuximab has a manageable safety profile and promising efficacy as second-line treatment in pts with R/M HNSCC. Biomarker data will be presented at the meeting."

Clinical • Combination therapy • IO biomarker • P1 data • Anemia • Cardiovascular • Congestive Heart Failure • Dermatitis • Dermatology • Endocrine Disorders • Head and Neck Cancer • Heart Failure • Hematological Disorders • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • SIRPA

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 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

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

Comprehensive biomarker and modeling approach to support dose finding for BI 836880, a VEGF/Ang-2 inhibitor. (PubMed, J Transl Med) - P1 | "The comprehensive analyses of multiple target engagement markers support BI 836880 720 mg q3w as a biologically relevant monotherapy dose schedule."

Biomarker • Journal • Oncology • Solid Tumor

Exploring new horizons in neovascular age-related macular degeneration: novel mechanisms of action and future therapeutic avenues. (PubMed, Eye (Lond)) - "Gene therapies, including RGX-314 and Ixo-vec, express an anti-VEGF protein, and 4D-150, expresses an anti-VEGF protein and a VEGF-C inhibitory miRNA. Anti-VEGF associated therapeutics include OPT-302, targeting VEGF-C and VEGF-D, BI 836880, which inhibits VEGF-A and Ang-2 activity, and Tarcocimab tedromer, inhibiting all VEGF-A isoforms. Agents with novel mechanisms of action include UBX1325, which inhibits an anti-apoptotic protein, Restoret (EYE103), a Wnt agonist, and the tyrosine kinase inhibitors, EYP-1901, OTX-TKI, CLS-AX, and KHK4951."

Journal • Review • Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • VEGFC • VEGFD

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

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 primary completion date: Nov 2024 ➔ Jul 2024

Combination therapy • Metastases • Trial primary completion date • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • SIRPA

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 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Jun 2024 ➔ May 2025 | Trial primary completion date: Jun 2024 ➔ May 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • 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 | Recruiting ➔ Active, not recruiting | Trial primary completion date: Apr 2025 ➔ Nov 2024

Combination therapy • Enrollment closed • Metastases • Trial primary completion date • Gastrointestinal Cancer • 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 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=45 | Recruiting | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Recruiting | Trial primary completion date: Aug 2024 ➔ Apr 2025

Combination therapy • Enrollment open • Metastases • Trial primary completion date • Gastrointestinal Cancer • 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 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=47 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Gastrointestinal Cancer • 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 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=45 | Recruiting | Sponsor: Boehringer Ingelheim | N=150 ➔ 45

Enrollment change • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Study to Test Different Doses of BI 836880 in Patients With an Eye Disease Called Wet Age-related Macular Degeneration (wAMD) (clinicaltrials.gov) - P1/2 | N=43 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

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=150 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Jul 2024 ➔ Jun 2025

Combination therapy • Metastases • Trial completion date • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Preclinical evaluation of the VEGF/Ang2 bispecific nanobody BI 836880 in nasopharyngeal carcinoma models. (PubMed, Invest New Drugs) - "When compared with bevacizumab, BI 836880 appeared to show at least comparable activity as bevacizumab in terms of its anti-proliferative and anti-angiogenic effects. This study showed that BI 836880 has anti-proliferative, anti-angiogenic and possibly immunomodulatory effect in clinical models of NPC, therefore the dual targeting of VEGF and Ang2 signaling in NPC should be further investigated."

Journal • Preclinical • Epstein-Barr Virus Infections • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • HIF1A • VEGFA

A Study to Test Different Doses of BI 836880 in Patients With an Eye Disease Called Wet Age-related Macular Degeneration (wAMD) (clinicaltrials.gov) - P1/2 | N=43 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Phase I study of the VEGF/Ang-2 inhibitor BI 836880 alone or combined with the anti-programmed cell death protein-1 antibody ezabenlimab in Japanese patients with advanced solid tumors. (PubMed, Cancer Chemother Pharmacol) - P1 | "MTD was not reached. BI 836880 alone and in combination with ezabenlimab had a manageable safety profile with preliminary clinical activity in Japanese patients with advanced solid tumors."

Journal • Metastases • P1 data • Cardiovascular • Hypertension • Oncology • Renal Disease • Solid Tumor

Phase Ib dose-escalation/expansion study of BI 836880, a VEGF/Ang2-blocking nanobody®, in combination with BI 754091, an anti-PD-1 antibody, in patients with advanced solid tumours (ESMO 2019) - P1; "Trial design:This open-label, dose-escalation/cohort-expansion trial is being conducted in two parts: Part 1, dose escalation of BI 836880 with BI 754091 in pts with advanced/metastatic, PD-L1 positive, nonsquamous NSCLC; Part 2, exploratory expansion cohorts (A–F) in 6 pt populations (A: metastatic [m] NSCLC after checkpoint inhibitor [CPI] monotherapy; B: mNSCLC after chemotherapy [CTX] + CPI; C: mSCLC after CTX with/without CPI; D: immunotherapy-resistant m-melanoma; E: recurrent glioblastoma after 1 st line CTX; F: hepatocellular carcinoma after prior sorafenib or lenvatinib with/without subsequent CPI therapy). Legal entity responsible for the study: Boehringer Ingelheim. Funding: Boehringer Ingelheim GmbH & Co, Ingelheim, Germany."

Clinical • Combination therapy • IO biomarker • P1 data • PD(L)-1 Biomarker • Brain Cancer • Gastrointestinal Cancer • Glioblastoma • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

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 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: May 2023 ➔ May 2024 | Trial primary completion date: May 2023 ➔ May 2024

Combination therapy • Trial completion date • Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Immune Modulation • Lung Cancer • Oncology • Solid Tumor

Ezabenlimab (BI 754091), an anti-PD-1 antibody, in combination with BI 836880, a VEGF/Ang2-blocking nanobody, in patients (pts) with advanced colorectal cancer (CRC). (ASCO-GI 2022) - P2 | "BI 836880 plus ezabenlimab had a manageable safety profile in pts with advanced MSS CRC; however, anti-tumor activity was limited in these pts, the majority of whom had received prior bevacizumab."

Clinical • Combination therapy • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase Ib study of BI 836880 (VEGF/Ang2 inhibitor) plus ezabenlimab (BI 754091; anti-PD-1 antibody) in patients (pts) with advanced hepatocellular carcinoma (HCC). (ASCO-GI 2022) - P1 | "BI 836880 + ezabenlimab had a manageable safety profile and showed promising activity in pts with untreated and second-line post-sorafenib/lenvatinib advanced HCC. Data continue to mature, particularly in cohort G. Cohort F has been expanded by a further 30 pts."

Clinical • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

[VIRTUAL] Phase Ib study evaluating BI 836880 (VEGF/Ang2 nanobody) in combination with ezabenlimab (BI 754091; anti-PD-1 antibody) in patients with solid tumours (ESMO 2021) - P1 | "Here, we report updated , including data from Part 2 (expansion cohorts). Part 2 has 7 cohorts: metastatic (m) NSCLC after checkpoint inhibitor (CPI) monotherapy (Cohort A); mNSCLC after chemotherapy (CT) + CPI (Cohort B); mSCLC after CT ± CPI (Cohort C); recurrent GBM (1st and 2nd recurrence; Cohort D); immunotherapy-resistant m-melanoma (Cohort E); HCC after prior sorafenib or lenvatinib (Cohort F); and previously untreated unresectable HCC (Cohort G). BI 836880 plus ezabenlimab had a manageable safety profile, with preliminary activity in a range of tumour types."

Clinical • Combination therapy • P1 data • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

[VIRTUAL] Ezabenlimab (BI 754091), an anti-PD-1 antibody, in combination with BI 836880, a VEGF/Ang2-blocking nanobody, in patients (pts) with previously treated advanced solid tumours (ESMO 2021) - P2 | "Ezabenlimab plus BI 836880 had a manageable safety profile and showed preliminary anti-tumour activity. Updated data will be presented."

Clinical • Combination therapy • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study to Test Different Doses of BI 836880 in Patients With an Eye Disease Called Wet Age-related Macular Degeneration (wAMD) (clinicaltrials.gov) - P1/2 | N=42 | Recruiting | Sponsor: Boehringer Ingelheim | Suspended ➔ Recruiting

Enrollment open • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration