Head and neck cancer lung cancer skincancer
Conditions
Interventions
Intravenous administration of:
[89Zr]Zr- BI 765063: Once 20mL (6 mg research drug)
BI 765063: Recommended dose for expansion (RDE) of FIH trial, administered
every 3 weeks (q3w).
BI 754091: 240 mg q
Sponsors
IQVIA RDS Netherlands B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Signed and dated, written informed consent form (ICF) prior to any trial-specific procedures 2. Male or female aged >= 18 years (no upper limit of age) at the time of ICF signature 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 4. Life expectancy of at least 3 months 5. For Arm A, only patients with a SIRPa polymorphism V1/V1 will be eligible; SIRPa polymorphism will be assessed in blood sampling (patient DNA) in a central laboratory; V1 allele is understood to include V1 and potential V1-like alleles. If, at a later time, V1/V2 heterozygous patients are considered for inclusion in this Arm of the trial, these patients will require to be centrally confirmed with at least one V1 allele. 6. Patients with histologically or cytologically documented advanced/metastatic primary or recurrent HNSCC, melanoma, NSCLC who failed or are not eligible to standard therapy 7. Patients with at least one measurable lesion are allowed as per RECIST v1.1 8. Patient must have at least one PET imageable and evaluable tumor lesion with a diameter of at least 20 mm 9. Patients must agree to on-treatment tumor biopsies (optional for first 3 patients in Part 1). 10. Adequate biological parameters defined as: • absolute neutrophil count (ANC) >= 1.5 x 109/L • hemoglobin (Hb) level >= 9 g/dL (without recent red blood cell transfusion within 2 weeks prior to study entry) • platelet count >= 100 x 109/L • total bilirubin level 50 mL/min (Chronic Kidney Disease Epidemiology [CKD-EPI] CKD-epi formula) • INR <= 1.5 (except if patient treated with anti-vitamin K); anticoagulation with anti-vitamin K and low molecular weight heparin [LMWH] is allowed 11. Prior major treatment-related surgery completed at least 28 days before study drug administration 12. Interval of at least 28 days or 5 half-lives (whichever is shorter) since the last chemotherapy, approved immunotherapy, biological or investigational therapy, radiation or tyrosine kinase inhibitor (TKI) therapy (e.g., sunitinib, sorafenib) must have elapsed before the first study drug administration(s) (on C1D1) and all toxicities related to previous anticancer therapies have resolved to normal value or <= Grade 1 prior to the study treatment administration (on C1D1), except alopecia 13. Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must agree to use highly effective methods of contraception (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly), prior to study entry, during the study and for 5 months after the last dose of study drug. A list of contraception methods meeting these criteria is provided in the patient information. The requirement of contraception does not apply to women of no childbearing potential and men not able to father a child, but they must have an evidence of such at screening. 14. Females of childbearing potential must have a serum negative pregnancy test within 7 days prior to first administration. Females who
Exclusion criteria
Exclusion criteria: 1. 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 study treatment administration, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period 2. 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) 3. Presence of other active invasive cancers other than the one treated in this trial within 5 years prior to screening (or less, pending discussion with sponsor), 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 4. 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 may be eligible 5. 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); 6. Patients receiving systemic treatment with any immunosuppressive medication within one-week prior to treatment start with SIRPa antibody (BI 765063 or BI 770371) and ezabenlimb; steroids of max. 10 mg prednisolone equivalent per day are allowed, topical and inhaled steroids are not considered as immunosuppressive 7. Patients who have interstitial lung disease or active, non-infectious pneumonitis. 8. Patients with uncontrolled disease-related metabolic disorders (e.g., hypercalcemia, SIADH) or uncontrolled diabetes 9. Patients 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) 10. Patients 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) 11. Patients 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 12. 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 administ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relative change from baseline (Cycle 1, up to Day 7) of peak Standardized Uptake Values (SUVs) of [89Zr]Zr-BI 765063 (arm A) or [89Zr]Zr-BI 770371 (arm B) in up to five target lesions at post BI 765063 (arm A) or BI 770371 (arm B) treatment scanning time points (Cycle 2, up to Day 7). | — |
Secondary
| Measure | Time frame |
|---|---|
| There is no secondary endpoint in this trial. | — |
Countries
Netherlands
Outcome results
None listed