A Study to Test Different Doses of BI 765049 Alone and in Combination With Ezabenlimab in Asian People With Advanced Cancer (Solid Tumours) Positive for B7-H6

NCT06091930 | Completed Phase 1

• 1 other identifier: 1454-0004
• Study Type: interventional
• Target: 21
• Locations: 3 countries
• Sites: 6

Brief Summary

This is a study in adults from Asia with different types of advanced cancer (solid tumours). People can join the study if they have cancer of the stomach, large bowel and rectum, pancreas, liver, head and neck or non-small cell lung cancer. This is a study for people for whom previous treatment was not successful or no treatment exists. People can participate if their tumour has the B7-H6 marker. The purpose of this study is to find the highest dose of BI 765049 that people with advanced cancer can tolerate when taken (alone and) together with ezabenlimab. Another purpose is to check whether BI 765049 taken (alone and) together with ezabenlimab can make tumours shrink. Both medicines may help the immune system fight cancer. Participants can stay in the study up to 3 years, as long as they can tolerate it and can benefit from it. During this time, they visit the study site about every 3 weeks. At the study site they get BI 765049 alone or in combination with ezabenlimab as an infusion into a vein. BI 765049 is given in 3-week cycles, ezabenlimab is given once every 3 weeks. The doctors check the health of the participants and note any health problems that could have been caused by BI 765049 or ezabenlimab. Doctors regularly check the size of the tumour and check whether it has spread to other parts of the body.

Conditions

Lung Cancer; Pancreatic Cancer; Colorectal Cancer; Head and Neck Cancer; Liver Cancer; Gastrointestinal Cancer

Outcome Measures

Primary Outcomes (4)

• Part I: Occurrence of dose-limiting toxicity (DLTs) during the maximum tolerated dose (MTD) evaluation period for BI 765049 monotherapy

  One treatment cycle, defined as 3 weeks after first administration of BI 765049 or 1 week after the administration of first full dose of BI 765049, whichever is longer

• Part II: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)

  Objective response will be determined by the Investigator in patients with measurable disease and will be defined as the best overall response of complete response (CR) or partial response (PR), from the first administration of trial medication until the earliest of progressive disease (PD), death, last evaluable tumour assessment before the start of subsequent anti-cancer therapy, lost to follow-up, or withdrawal of consent.

  Up to month 36

• Part III: Occurrence of dose-limiting toxicity (DLTs) during the maximum tolerated dose (MTD) evaluation period for BI 765049 in combination with ezabenlimab

  From first BI 765049 administration to 1 week after the first ezabenlimab dose

• Part IV: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)

  Up to month 36

Secondary Outcomes (26)

• Part I: Maximum measured concentration of BI 765049 (Cmax) after first administration

  Up to 1 day

• Part I: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations

  Up to month 37

• Part III: Maximum measured concentration of BI 765049 (Cmax) after the first administration

  Up to 1 day

• Part III: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations

  Up to month 37

• Part I: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after the first administration

  Up to 1 day

Study Arms (4)

Part I: BI 765049

EXPERIMENTAL

BI 765049 monotherapy - dose escalation

Drug: BI 765049

Part II: BI 765049

EXPERIMENTAL

BI 765049 monotherapy - dose expansion

Drug: BI 765049

Part III: BI 765049 + ezabenlimab

EXPERIMENTAL

BI 765049 + ezabenlimab combination therapy - dose escalation

Drug: BI 765049; Drug: Ezabenlimab

Part IV: BI 765049 + ezabenlimab

EXPERIMENTAL

BI 765049 + ezabenlimab combination therapy - dose expansion

Drug: BI 765049; Drug: Ezabenlimab

Interventions

Ezabenlimab DRUG

Ezabenlimab

Also known as: BI 754091

Part III: BI 765049 + ezabenlimab; Part IV: BI 765049 + ezabenlimab

BI 765049 DRUG

BI 765049

Part I: BI 765049; Part II: BI 765049; Part III: BI 765049 + ezabenlimab; Part IV: BI 765049 + ezabenlimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated, written inform consent form (ICF) (ICF1 for B7-H6 testing for all patients except those with colorectal cancer (CRC); ICF2 for all patients) describing the study in accordance with International Council on Harmonisation Good Clinical Practice (ICH-GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses.
• ≥18 years of age at the time of signature on the ICFs (ICF1 and ICF2).
• Histologically or cytologically confirmed diagnosis of an advanced, unresectable, and/or metastatic gastrointestinal cancer, colorectal cancer, pancreatic cancer, liver cancer, head and neck cancer, or lung cancer.
• Disease progression despite conventional treatment, intolerant to or not a candidate for conventional treatment, or with a tumour for which no conventional treatment exists.
• Agree to the collection of tumour samples (as slides from archival diagnostic samples or fresh tumour biopsies) for confirmation of B7-H6 expression at Screening Visit 02 for colorectal cancer (CRC) patients or at Screening Visit 01 for all other patients.
• Confirmed B7-H6 expression on tumour tissue sample (archived or fresh tumour biopsy) based on central pathology review except for patients diagnosed with advanced or metastatic colorectal cancer (CRC).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• At least one evaluable target lesion as defined per response evaluation criteria in solid tumors (RECIST v1.1), outside of the central nervous system (CNS), separate from any lesion(s) identified for tumour biopsy. Tumour lesions that have been irradiated ≥28 days before the start of treatment, and have subsequently had documented progression, may be chosen as target lesions only in the absence of measurable lesions that have not been irradiated.

You may not qualify if:

• History of a major surgery within 28 days prior to first dose of BI 765049 (major according to the Investigator's assessment).
• Previous or concomitant malignancies other than the one treated in this trial within the last 3 years except:
• Effectively treated non-melanoma skin cancers
• Effectively treated carcinoma in situ of the cervix
• Effectively treated ductal carcinoma in situ
• Other effectively treated malignancy that is considered cured by local treatment
• Known leptomeningeal disease or spinal cord compression due to disease.
• Require anticoagulant treatment which cannot be safely interrupted, if medically needed for a study procedure (e.g., biopsy) based on the opinion of the Investigator.
• Hepatitis C virus (HCV) infection, defined as:
• Currently receiving curative antiviral treatment for HCV infection, and/or
• HCV viral load is above the limit of quantification (HCV Ribonucleic acid (RNA) positive)
• Hepatitis B virus (HBV) infection with the following laboratory evidence: positive results of hepatitis B surface (HBs) antigen and presence of Hepatitis B core (HBc) antibody together with HBV-deoxyribonucleic acid (DNA).
• Presence of any infection requiring systemic antimicrobial treatment within 7 days prior to first dose of trial medication. Patients who have any clinical signs of infection (e.g. fever or leukocytosis) within 48 hours prior to first dose of trial medication are not eligible.
• Patients with known history of human immunodeficiency virus (HIV) infection who meet one or more of the following criteria:
• Cluster of differentiation 4 (CD4+) count \<350 cells/μL (local lab assessment)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (6)

Shanghai East Hospital

Shanghai, 200120, China

Location

National Cancer Center Hospital East

Chiba, Kashiwa, 277-8577, Japan

Location

National Cancer Center Hospital

Tokyo, Chuo-ku, 104-0045, Japan

Location

Japanese Foundation for Cancer Research

Tokyo, Koto-ku, 135-8550, Japan

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Related Links

• Related Info

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Colorectal Neoplasms; Head and Neck Neoplasms; Liver Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: All trial parts will be conducted open label.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The trial is divided in four parts. Part I and Part III will have a sequential assignment while Part II and Part IV will have a parallel assignment.

Study Record Dates

• First Submitted: October 16, 2023
• First Posted: October 23, 2023
• Study Start: February 16, 2024
• Primary Completion: August 15, 2025
• Study Completion: October 3, 2025
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

JP (3); KR (2); CN (1)