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

NCT05249426 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 1443-00022021-003473-59
• Study Type: interventional
• Target: 48
• Locations: 11 countries
• Sites: 25

Brief Summary

With an amendment of the protocol, this study is only open to adults with head and neck cancer. Previously also adults with liver cancer joined. This is a study for people for whom previous treatment was not successful or no standard treatment exists. The purpose of this study is to find out whether combining different medicines make tumours shrink. The tested medicines in this study are antibodies that act in different ways against cancer. BI 765063 and ezabenlimab may help the immune system fight cancer (checkpoint inhibitors). Cetuximab blocks growth signals and may prevent the tumour from growing. BI 836880 blocks the formation of new blood vessels that the tumour needs to grow. With amendments of the protocol, all participants receive cetuximab in addition to BI 765063 and ezabenlimab. Ezabenlimab treatment and any other assigned treatment are given no longer than 2 years. Previously, BI 765063 and ezabenlimab were also given alone, or in combination with chemotherapy, or with BI 836880. BI 765063, ezabenlimab, and BI 836880 are given as infusions into veins every 3 weeks. Cetuximab is given as an infusion every 1 or 2 weeks. Participants can stay in the study as long as they benefit from treatment and can tolerate it. They regularly visit the study site where doctors check participants' health and take note of any unwanted effects. The doctors also monitor the size of the tumour.

Conditions

Head and Neck Squamous Cell Carcinoma (HNSCC)

Outcome Measures

Primary Outcomes (1)

• Objective Response (OR)

  Objective response (OR) with confirmation, defined as the best overall response of complete response (CR) or partial response (PR), where best overall response is determined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1) by investigator's assessment from first treatment administration until the earliest of disease progression, death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, lost to follow-up or withdrawal of consent.

  Up to 24 months.

Secondary Outcomes (4)

• Occurrence of treatment emergent adverse events (AEs)

  Up to 24 months.

• Duration of objective response (DOR)

  Up to 24 months.

• Disease control (DC)

  Up to 24 months.

• Progression-free survivial (PFS)

  Up to 24 months.

Study Arms (5)

Cohort A: BI 765063 + ezabenlimab + cetuximab

EXPERIMENTAL

30 Signal Regulatory Protein Alpha (SIRPα) V1/V1 homozygous patients with 2nd line recurrent/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) who had received prior platinum-based therapy within the recurrent/metastatic setting.

Drug: BI 765063; Drug: Ezabenlimab; Drug: Cetuximab

Cohort B: BI 765063 + ezabenlimab + chemo (invest choice)

EXPERIMENTAL

30 SIRPα V1/V1 homozygous patients with 2nd line recurrent/metastatic HNSCC who had received prior platinum-based therapy within the recurrent/metastatic setting.

Drug: BI 765063; Drug: Ezabenlimab; Other: Investigator´s Choice Chemotherapy

Cohort C: BI 765063 + ezabenlimab

EXPERIMENTAL

30 SIRPα V1/V1 homozygous patients with advanced or metastatic 1st line Hepatocellular Carcinoma (HCC).

Drug: BI 765063; Drug: Ezabenlimab

Cohort D: BI 765063 + ezabenlimab + BI 836880

EXPERIMENTAL

30 SIRPα V1/V1 homozygous patients with advanced or metastatic 1st line HCC.

Drug: BI 765063; Drug: Ezabenlimab; Drug: BI 836880

Cohort E: BI 765063 + ezabenlimab + BI 836880

EXPERIMENTAL

30 SIRPα V1/V1 homozygous patients with advanced or metastatic 2nd line HCC who progressed on therapy with atezolizumab in combination with bevacizumab.

Drug: BI 765063; Drug: Ezabenlimab; Drug: BI 836880

Interventions

BI 765063 DRUG

BI 765063 (anti-Signal Regulatory Protein Alpha (SIRPα) Monoclonal Antibody (mAb))

Cohort A: BI 765063 + ezabenlimab + cetuximab; Cohort B: BI 765063 + ezabenlimab + chemo (invest choice); Cohort C: BI 765063 + ezabenlimab; Cohort D: BI 765063 + ezabenlimab + BI 836880; Cohort E: BI 765063 + ezabenlimab + BI 836880

Ezabenlimab DRUG

Ezabenlimab (anti-Programmed cell death protein 1 (PD-1) Monoclonal Antibody (mAb))

Also known as: BI 754091

Cohort A: BI 765063 + ezabenlimab + cetuximab; Cohort B: BI 765063 + ezabenlimab + chemo (invest choice); Cohort C: BI 765063 + ezabenlimab; Cohort D: BI 765063 + ezabenlimab + BI 836880; Cohort E: BI 765063 + ezabenlimab + BI 836880

BI 836880 DRUG

BI 836880 (anti-Vascular Endothelial Growth Factor (VEGF) / Angiopoetin 2 (Ang2))

Cohort D: BI 765063 + ezabenlimab + BI 836880; Cohort E: BI 765063 + ezabenlimab + BI 836880

Cetuximab DRUG

Cetuximab

Cohort A: BI 765063 + ezabenlimab + cetuximab

Investigator´s Choice Chemotherapy OTHER

Allowable chemotherapies include: paclitaxel, docetaxel, capecitabine, 5-fluorouracil, methotrexate or combinations thereof

Cohort B: BI 765063 + ezabenlimab + chemo (invest choice)

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form (ICF) prior to any trial-specific procedures.
• Male or female aged ≥ 18 years at the time of ICF signature.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the screening visit.
• Expected life expectancy of at least 3 months.
• Patients homozygous for V1 allele (including V1-like alleles) of Singal Regulatory Protein-alpha (SIRPα) (V1/V1 SIRPα genotype). SIRPα polymorphism will be assessed in blood sampling (using patient Deoxyribonucleic Acid \[DNA\]) during Screening 1 Visit.
• Patients with at least one measurable lesion as per Response Evaluation Critiera In Solid Tumours (RECIST) version 1.1 (v1.1).
• Patients must agree to provide a mandatory pre-treatment (baseline) biopsy and an ontreatment fresh tumour biopsy (unless medically contraindicated. or mandatory requirement is lifted by the sponsor). Details on biopsy sample collection are provided in the Lab Manual.
• \-- Pre-treatment (baseline) biopsy: A fresh tumour biopsy before receiving the trial medication is preferred. In case a fresh tumour biopsy cannot be obtained, the Sponsor must be notified and archival formalin-fixed paraffin embedded (FFPE) tumour tissue block from the most recent time point before entering the trial must be provided (maximum 6 months prior to study entry). If these requirements cannot be met, the patient may still be allowed to enter the study at the discretion of the sponsor, after discussion between the Investigator and Sponsor.
• Female patients. Women of childbearing potential (WOCBP) must agree to use highly effective methods of contraception per ICH M3 (R2), that results in a less than 1% per year failure rate when used consistently and correctly, starting at the screening visit, during the trial and for 6 months after the end of trial treatment. The requirement of contraception does not apply to women of no childbearing potential, but they must have evidence of such at screening. Women of childbearing potential must have a serum negative pregnancy test within 72 hours prior to first drug administration.
• Women who are postmenopausal for at least 1 year (defined as more than 12 months since last menses) or are surgically sterilized do not require this test. The following methods of contraception are considered highly effective:
• Combined (oestrogen and progestogen containing) hormonal birth control that prevents ovulation (oral, intravaginal, transdermal)
• Progestogen-only hormonal birth control that prevents ovulation (oral, injectable, implantable)
• Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomised partner (provided that this is the sole sexual partner and has received medical assessment of the surgical success)

You may not qualify if:

• Patients with at least one SIRPα V2 allele, i.e. SIRPα V1/V2 or V2/V2 individuals.
• Patients with symptomatic/active central nervous system (CNS) metastases. Patients with previously treated brain metastases are eligible, if there is no evidence of progression for at least 28 days before the first trial drug administration without requirement for treatment with corticosteroids, as ascertained by clinical examination and brain imaging (MRI (magnetic resonance imaging) or CT (computed tomography)) during the screening period.
• Prior allogeneic stem cell or solid organ transplantation.
• Any tumour location necessitating an urgent therapeutic intervention (e.g., palliative care, surgery or radiation therapy, such as spinal cord compression, other compressive mass, uncontrolled painful lesion, bone fracture).
• Presence of active invasive cancers other than the one treated in this trial within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin, or in situ carcinoma of uterine cervix, or other local tumours considered cured by local treatment.
• Patients with active autoimmune disease or a documented history of autoimmune disease, that requires systemic treatment, i.e. corticosteroids or immunosuppressive drugs, except patients with vitiligo, resolved childhood asthma/atopy, alopecia, or any chronic skin condition that does not require systemic therapy; patients with autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and/or controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible.
• History of severe hemorrhagic or thromboembolic event in the past 12 months (excluding central venous catheter thrombosis, peripheral deep vein thrombosis and portal vein thrombosis due to HCC tumor invasion).
• Known prior history of severe infusion related reactions to monoclonal antibodies (Grade ≥ 3 National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events (CTCAE) v5.0).

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (25)

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

Location

CTR Georges-François Leclerc

Dijon, 21079, France

Location

CTR Leon Berard

Lyon, 69373, France

Location

HOP Timone

Marseille, 13385, France

Location

INS Curie

Paris, 75248, France

Location

HOP Civil

Strasbourg, 67091, France

Location

INS Claudius Regaud IUCT-Oncopole

Toulouse, 31059, France

Location

Japanese Foundation for Cancer Research

Tokyo, Koto-ku, 135-8550, Japan

Location

Hospital Sultan Ismail

Johor Bahru, 81100, Malaysia

Location

Sarawak General Hospital

Kuching, Sarawak, 93586, Malaysia

Location

ARKE SMO S.A. de C.V

Mexico City, 06700, Mexico

Location

FAICIC S de RL de C.V.

Veracruz, 91900, Mexico

Location

Investigacion Biomedica para el Desarrollo de Farmacos, S.A. de C.V.

Zapopan, 45070, Mexico

Location

ARENSIA Exploratory Medicine

Chisinau, MD-2025, Moldova

Location

Mandziuk Slawomir Specialist Medical Practice

Lublin, 20-093, Poland

Location

"Prof. Dr. Alexandru Trestioreanu" Oncology Institut

Bucharest, 022328, Romania

Location

Institute Of Oncology Prof. Dr. Ion Chiricuta Cluj-Napoca

Cluj-Napoca, 400015, Romania

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08907, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

The Royal Marsden Hospital, London

London, SW3 6JJ, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Partly randomized trial. Patients will be randomized into cohort A, B, C and D. No randomization in cohort E.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2022
• First Posted: February 21, 2022
• Study Start: April 12, 2022
• Primary Completion: July 15, 2024
• Study Completion (Estimated): July 31, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

RO (2); FR (6); ME (3); GB (3); JP (1); MO (1); US (1); MY (2); ES (3); PL (1); TH (2)