Clinical trial NCT06091930: 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
Official title: Phase I, Non-randomised, Open-label, Multi-centre Dose Escalation and Expansion Trial of BI 765049 and BI 765049 + Ezabenlimab Administered by Repeated Intravenous Infusion in Asian Patients With Malignant Solid Tumours Expressing B7-H6
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Gastrointestinal Cancer
Lung Cancer
Pancreatic Cancer
Colorectal Cancer
Head and Neck Cancer
Liver Cancer
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2023-10-23
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.
* Further inclusion criteria apply

Exclusion Criteria:

* 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)
  * Viral load \>400 copies/mL (local lab assessment)
  * Not receiving antiretroviral therapy
  * Receiving established antiretroviral therapy for less than four weeks prior to the start of study treatment
  * History of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within 12 months prior to start of study treatment Patients with a history of HIV who do not meet any of the criteria above are eligible to participate, but the patient must be under the care of a HIV/Infectious Diseases specialist, or a HIV/Infectious Diseases specialist must be consulted prior to inclusion.
* Further exclusion criteria apply

Primary outcomes:
measure: Part I: Occurrence of dose-limiting toxicity (DLTs) during the maximum tolerated dose (MTD) evaluation period for BI 765049 monotherapy
timeFrame: 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
measure: Part II: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)
timeFrame: Up to month 36
measure: Part III: Occurrence of dose-limiting toxicity (DLTs) during the maximum tolerated dose (MTD) evaluation period for BI 765049 in combination with ezabenlimab
timeFrame: From first BI 765049 administration to 1 week after the first ezabenlimab dose
measure: Part IV: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)
timeFrame: Up to month 36
Secondary outcomes:
measure: Part I: Maximum measured concentration of BI 765049 (Cmax) after first administration
timeFrame: Up to 1 day
measure: Part I: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations
timeFrame: Up to month 37
measure: Part III: Maximum measured concentration of BI 765049 (Cmax) after the first administration
timeFrame: Up to 1 day
measure: Part III: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations
timeFrame: Up to month 37
measure: Part I: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after the first administration
timeFrame: Up to 1 day
measure: Part I: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after multiple administrations
timeFrame: Up to month 37
measure: Part III: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after the first administration
timeFrame: Up to 1 day
measure: Part III: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after multiple administrations
timeFrame: Up to month 37
measure: Part I: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)
timeFrame: Up to month 36
measure: Part III: Objective response based on the response evaluation criteria in solid tumors (RECIST v1.1)
timeFrame: Up to month 36
measure: Part II: Progression free survival (PFS)
timeFrame: Up to month 36
measure: Part IV: Progression free survival (PFS)
timeFrame: Up to month 36
measure: Part II: Duration of response
timeFrame: Up to month 36
measure: Part IV: Duration of response
timeFrame: Up to month 36
measure: Part II: Disease control
timeFrame: Up to month 36
measure: Part IV: Disease control
timeFrame: Up to month 36
measure: Part II: Objective response based on the immune response evaluation criteria in solid tumors (iRECIST)
timeFrame: Up to month 36
measure: Part IV: Objective response based on the immune response evaluation criteria in solid tumors (iRECIST)
timeFrame: Up to month 36
measure: Part II: Maximum measured concentration of BI 765049 (Cmax) after first administration
timeFrame: Up to 1 day
measure: Part II: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations
timeFrame: Up to month 37
measure: Part IV: Maximum measured concentration of BI 765049 (Cmax) after first administration
timeFrame: Up to 1 day
measure: Part IV: Maximum measured concentration of BI 765049 (Cmax) after multiple administrations
timeFrame: Up to month 37
measure: Part II: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after first administration
timeFrame: Up to 1 day
measure: Part II: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after multiple administrations
timeFrame: Up to month 37
measure: Part IV: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after first administration
timeFrame: Up to 1 day
measure: Part IV: Area under the concentration-time curve of BI 765049 over a uniform dosing interval τ (AUCτ) after multiple administrations
timeFrame: Up to month 37
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Shanghai
country: China
facility: Shanghai East Hospital
city: Chiba, Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Tokyo, Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Tokyo, Koto-ku
country: Japan
facility: Japanese Foundation for Cancer Research
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
References: