A Trial of BI 765063 Monotherapy and in Combination With BI 754091 in Patients With Advanced Solid Tumours

NCT03990233 | Completed Phase 1 DMC

• 2 other identifiers: 1443-00012018-003830-34
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 8

Brief Summary

This trial will be a two steps Phase I clinical study in patients with advanced solid tumors with an escalating phase (Step 1) followed by an expansion phase (Step 2) of BI 765063, a monoclonal antibody (mAb) antagonist to signal regulatory protein alpha (SIRPα) receptor, a myeloid checkpoint inhibitor administered as single agent, and in combination with BI 754091, a mAb antagonist to PD-1 receptor, a lymphocyte T checkpoint inhibitor.

Conditions

Solid Tumor, Adult

Keywords

Checkpoint inhibitor (ICI); SIRPα; Advanced solid tumors; Anti-PD-1

Outcome Measures

Primary Outcomes (3)

• Step 1 (dose escalation Parts A and B): Number of patients with Dose-Limiting Toxicities (DLTs) during the first treatment cycle

  3 weeks (1 cycle)

• Step 1 (dose escalation Parts A and B): Maximum Tolerated Dose (MTD) determination

  3 weeks (1 cycle)

• Step 2 (expansion combination Part C): Number of patients with DLT-like events during the whole treatment

  An average of 1 year

Secondary Outcomes (6)

• Step 1: Number of patients with DLT-like events during the whole treatment

  An average of 1 year

• Step 1 and 2: Incidence and severity of all Adverse Events (AEs), Serious AEs (SAEs), AEs of special interest (AESIs), Immune related AEs (irAEs)

  An average of 1 year

• Step 2: Objective Response Rate (ORR) defined as best response of Complete Response (CR) and Partial Response (PR) as per RECIST v 1.1 and immune RECIST (iRECIST) criteria

  An average of 1 year

• Step 1 and 2: Cmax determination

  12 weeks (4 cycles)

• Step 1 and 2: AUC 0-tz determination

  Up to 12 weeks (4 cycles)

Study Arms (4)

Step 1 (Dose escalation) : Cohorts A

EXPERIMENTAL

BI 765063 (SIRPα inhibitor) alone in V1/V1 homozygous and V1/V2 heterozygous patients with advanced solid tumours

Drug: BI 765063

Step 1 (Dose escalation) : Cohorts B

EXPERIMENTAL

BI 765063 (SIRPα inhibitor) in combination with BI 754091 (PD-1 inhibitor) in V1/V1 homozygous and V1/V2 heterozygous patients with advanced solid tumours

Drug: BI 765063; Drug: BI 754091

Step 2 (Expansion Cohorts) : Cohort C1

EXPERIMENTAL

BI 765063 (SIRPα inhibitor) in combination with BI 754091 (PD-1 inhibitor) in V1/V1 homozygous patients with metastatic colorectal cancer

Drug: BI 765063; Drug: BI 754091

Step 2 (Expansion Cohorts) : Cohort C2

EXPERIMENTAL

BI 765063 (SIRPα inhibitor) in combination with BI 754091 (PD-1 inhibitor) in V1/V1 homozygous patients with metastatic endometrium cancer

Drug: BI 765063; Drug: BI 754091

Interventions

BI 765063 DRUG

mAb antagonist to SIRPα receptor, a myeloid checkpoint inhibitor

Also known as: OSE-172

Step 1 (Dose escalation) : Cohorts A; Step 1 (Dose escalation) : Cohorts B; Step 2 (Expansion Cohorts) : Cohort C1; Step 2 (Expansion Cohorts) : Cohort C2

BI 754091 DRUG

mAb antagonist to PD-1 receptor, a lymphocyte T checkpoint inhibitor

Step 1 (Dose escalation) : Cohorts B; Step 2 (Expansion Cohorts) : Cohort C1; Step 2 (Expansion Cohorts) : Cohort C2

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 informed consent form (ICF) prior to any trial-specific procedures.
• Male or female aged ≥ 18 years (no upper limit of age) at the time of ICF signature.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least 3 months.
• Patients with a SIRPα polymorphism including at least one V1 allele will be selected (i.e., homozygous V1/V1 or heterozygous V1/V2 in separate cohorts in escalation \[Step 1\] and only homozygous V1/V1 in expansion cohorts \[Step 2\]); SIRPα polymorphism will be assessed in blood sampling (patient DNA) in a central laboratory; V1 allele is understood to include V1 and V1-like alleles.
• In Step 1: Patients with histologically or cytologically documented advanced/metastatic primary or recurrent malignancies who failed or are not eligible to standard therapy;
• In Step 2: Cohort C1: Patients with histologically or cytologically advanced/metastatic primary or recurrent unresectable documented MSS colorectal tumors, whose disease relapsed after standard of care and who received no prior anti-PD-L1 inhibitors.
• Cohort C2: Patients with histologically or cytologically advanced or metastatic documented MSS endometrial carcinoma whose disease relapsed after standard of care and who received no prior anti-PD-L1 inhibitors.
• Patients with at least one measurable lesion as per RECIST v1.1.
• Patients must agree to pre- and on-treatment tumor biopsies. Fresh tumor biopsy may come either from the primary tumor or from a metastasis. Cytological material is not accepted. Archival tumor biopsy is acceptable, if done within 4 weeks before the first treatment administration.
• Biopsy sites should be carefully selected by the investigator so that it is safe for the patient and subsequent biopsy can be performed at the same location; also if possible should be distinct from the measurable lesion;
• Adequate biological parameters defined as:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L.
• Hemoglobin (Hb) level ≥ 10 g/dL. (without recent red blood cell transfusion within 2 weeks prior to study entry)
• Platelet count ≥ 100 x 10\^9/L.

You may not qualify if:

• Patient with symptomatic/active central nervous system (CNS) metastases; Patient with previously treated brain metastases are eligible, if there is no evidence of progression for at least 28 days before the first study treatment administration, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period;
• Other tumor 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 other 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 tumors considered cured by local treatment;
• Patient 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 may be eligible.
• Known severe infusion related reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v5.0) and patients removed from previous anti-PD-1 or anti-PD-L1 therapy because of a severe or life-threatening immune-related adverse event (irAE) (Grade ≥ 3 NCI-CTCAE v5.0);
• Patients receiving systemic treatment with any immunosuppressive medication within one-week prior treatment start; Steroids of max. 10 mg prednisolone equivalent per day are allowed, topical and inhaled steroids are not considered as immunosuppressive.
• Patients with interstitial lung disease or active, non-infectious pneumonitis.
• Patient with uncontrolled disease-related metabolic disorders (e.g., hypercalcemia, SIADH) or uncontrolled diabetes;
• Patient with uncontrolled congestive heart failure defined as New York Heart Association (NYHA) class III or IV, uncontrolled hypertension, unstable heart disease (e.g., coronary artery disease with unstable angina or myocardial infarction within 6 months before study treatment administration).
• Patient with significant ECG abnormalities defined as any cardiac dysrhythmia (\> Grade 2) (i.e., significant ventricular arrhythmia as persistent ventricular tachycardia and/or ventricular fibrillation; severe conduction disorders as atrio-ventricular block 2 and 3, sino-atrial block) or baseline QT/QTc interval \>480 milliseconds (ms).
• Patient with significant chronic liver disease (e.g., significant fibrosis, known cirrhosis) or active HBV or HCV infection; If HbsAg positive, an effective antiviral treatment to prevent hepatitis B reactivation is recommended.
• Patients with known Human Immunodeficiency Virus (HIV) infection or patients with an active infection requiring specific anti-infective therapy until all signs of infection have resolved, and this within 2 weeks prior to the first study treatment administration;
• Patient whose medical, psychological including alcohol or drug abuse, or surgical conditions are unstable and may affect the study completion and/or compliance and/or the ability to give informed consent.

Sponsors & Collaborators

• OSE Immunotherapeutics: lead
• Boehringer Ingelheim: collaborator

Study Sites (8)

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Universitair Ziekenhuis Brussel

Brussels, 1000, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Hospital St Pierre

La Réunion, France

Location

Centre Léon Berard

Lyon, 69373, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * Step 1 (Dose escalation \[Cohorts A and B\]) primary objective : In V1/V1 homozygous and V1/V2 heterozygous patients with advanced solid tumors, Dose-Limiting Toxicities (DLTs), Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of BI 765063, as monotherapy (Cohort A) and in combination with BI 754091 (Cohort B). * Step 2 (Expansion Cohorts \[Cohorts C\]) primary objective : In V1/V1 homozygous patients with selected advanced solid tumors (colorectal or endometrium), DLT-like events and RP2D confirmation of BI 765063 in combination with BI 754091.

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: June 18, 2019
• Study Start: April 16, 2019
• Primary Completion: April 17, 2023
• Study Completion: April 30, 2025
• Last Updated: June 26, 2025

Record last verified: 2025-06

Locations

FR (5); BE (3)