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

NCT ID: NCT05249426

Last Updated: 2026-01-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-12

Study Completion Date

2026-07-31

Brief Summary

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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.

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Detailed Description

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Conditions

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Head and Neck Squamous Cell Carcinoma (HNSCC)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Partly randomized trial. Patients will be randomized into cohort A, B, C and D. No randomization in cohort E.

Study Groups

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Cohort A: BI 765063 + ezabenlimab + cetuximab

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.

Group Type EXPERIMENTAL

BI 765063

Intervention Type DRUG

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

Ezabenlimab

Intervention Type DRUG

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

Cetuximab

Intervention Type DRUG

Cetuximab

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

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

Group Type EXPERIMENTAL

BI 765063

Intervention Type DRUG

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

Ezabenlimab

Intervention Type DRUG

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

Investigator´s Choice Chemotherapy

Intervention Type OTHER

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

Cohort C: BI 765063 + ezabenlimab

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

Group Type EXPERIMENTAL

BI 765063

Intervention Type DRUG

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

Ezabenlimab

Intervention Type DRUG

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

Cohort D: BI 765063 + ezabenlimab + BI 836880

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

Group Type EXPERIMENTAL

BI 765063

Intervention Type DRUG

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

Ezabenlimab

Intervention Type DRUG

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

BI 836880

Intervention Type DRUG

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

Cohort E: BI 765063 + ezabenlimab + BI 836880

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

Group Type EXPERIMENTAL

BI 765063

Intervention Type DRUG

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

Ezabenlimab

Intervention Type DRUG

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

BI 836880

Intervention Type DRUG

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

Interventions

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BI 765063

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

Intervention Type DRUG

Ezabenlimab

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

Intervention Type DRUG

BI 836880

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

Intervention Type DRUG

Cetuximab

Cetuximab

Intervention Type DRUG

Investigator´s Choice Chemotherapy

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

Intervention Type OTHER

Other Intervention Names

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BI 754091

Eligibility Criteria

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Inclusion Criteria

* 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)
* Sexual abstinence (if accepted by local ethics boards and regulatory agencies as highly effective) Sexual abstinence is defined as refraining from heterosexual intercourse during the entire study period from screening through 6 months after last trial treatment. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.

Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception for use during this trial.

Although use of a contraceptive pill and Intrauterine device (IUD) together are considered a highly- effective method of birth control, women of childbearing potential taking a contraceptive pill must use an additional barrier method for the entire duration of the trial treatment intake and for 6 months after the end of the trial treatment intake. WOCBP is defined as: fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Tubal ligation is NOT a method of permanent sterilisation. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.

Exclusion Criteria

* 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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Valkyrie Clinical Trials

Los Angeles, California, United States

Site Status

CTR Georges-François Leclerc

Dijon, , France

Site Status

CTR Leon Berard

Lyon, , France

Site Status

HOP Timone

Marseille, , France

Site Status

INS Curie

Paris, , France

Site Status

HOP Civil

Strasbourg, , France

Site Status

INS Claudius Regaud IUCT-Oncopole

Toulouse, , France

Site Status

Japanese Foundation for Cancer Research

Tokyo, Koto-ku, , Japan

Site Status

Hospital Sultan Ismail

Johor Bahru, , Malaysia

Site Status

Sarawak General Hospital

Kuching, Sarawak, , Malaysia

Site Status

ARKE SMO S.A. de C.V

Mexico City, , Mexico

Site Status

FAICIC S de RL de C.V.

Veracruz, , Mexico

Site Status

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

Zapopan, , Mexico

Site Status

ARENSIA Exploratory Medicine

Chisinau, , Moldova

Site Status

Mandziuk Slawomir Specialist Medical Practice

Lublin, , Poland

Site Status

"Prof. Dr. Alexandru Trestioreanu" Oncology Institut

Bucharest, , Romania

Site Status

Institutul Oncologic "Prof. Dr. Ion Chiricuta"

Cluj-Napoca, , Romania

Site Status

Hospital Universitari Vall D Hebron

Barcelona, , Spain

Site Status

Hospital Duran i Reynals

L'Hospitalet de Llobregat, , Spain

Site Status

Hospital Clínico San Carlos

Madrid, , Spain

Site Status

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Site Status

Songklanagarind Hospital

Songkhla, , Thailand

Site Status

King's College Hospital

London, , United Kingdom

Site Status

The Royal Marsden Hospital, Chelsea

London, , United Kingdom

Site Status

Hammersmith Hospital

London, , United Kingdom

Site Status

Countries

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United States France Japan Malaysia Mexico Moldova Poland Romania Spain Thailand United Kingdom

Related Links

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Other Identifiers

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2021-003473-59

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1443-0002

Identifier Type: -

Identifier Source: org_study_id

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