Phase I Study of BCD-145 (Anti-CTLA-4) in Patients With Unresectable/Metastatic Melanoma

Study Overview
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Brief Summary
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A Multicenter Open-Label Single-Arm Multi-Cohort Phase I Study of Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of BCD-145 (JSC BIOCAD, Russia) Monotherapy in Patients with Unresectable/Metastatic Melanoma.

Official Title
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A Multicenter Open-Label Single-Arm Multi-Cohort Phase I Study of Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of BCD-145 (JSC BIOCAD, Russia) in Patients With Unresectable/Metastatic Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Biological: BCD-145


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient provides a written informed consent and is able to follow the requirements of the Protocol; Age ≥ 18 years Histologically confirmed (well-documented test results; preferably, block specimens available) unresectable (stage III/IV) or metastatic (stage IV) melanoma (the drug will be used as the first of subsequent therapy lines); ECOG score of 0 to 2; Measurable disease (at least one lesion) according to RECIST v1.1 ; Resolved toxicity events from the previous therapy or adverse consequences of surgical interventions to ≤ grade 1 CTCAE v. 4.03, except for chronic/irreversible adverse events not affecting the safety of the study therapy (e.g. alopecia); No severe pathology of organs or systems; Life expectancy of at least 16 weeks from the screening; Patients of childbearing potential enrolled in the study must agree to use reliable contraception methods throughout the study period, beginning 2 weeks before the inclusion in the study and up to 8 weeks after the last dose of BCD-145. Exclusion Criteria: Severe concomitant illnesses or life-threatening consequences (including pleural/pericardial/peritoneal effusion that requires medical intervention , pulmonary lymphangitis, or involvement of >50% renal parenchyma); Brain metastases ; Severe cardiovascular disorders within 6 months before screening; Autoimmune diseases; Conditions requiring steroids or any other immunosuppressants; Blood disorders: ANC ≤1,500/mm3; platelets ≤100,000/mm3; or Hb ≤90 g/L; Renal function impairment: creatinine ≥1.5 × ULN; Hepatic function impairment: bilirubin ≥1.5 × ULN; AST and ALT ≥2.5 × ULN (5 × ULN for patients with liver metastases), AlkPh ≥ 5 × ULN; Endocrine disorders: abnormal thyroid hormones Prior anticancer treatment within 28 days before starting the study drug (surgery, radiation therapy , or chemotherapy); Known history of more than 6 lines of systemic anticancer chemotherapy (including neoadjuvant and adjuvant CTs); Prior treatment with anti-PD1/PDL1 agents or CTLA4 inhibitors; Concurrent malignancy except for radically resected cervical carcinoma in situ or radically resected basal cell/squamous cell carcinoma; Conditions limiting patient's ability to follow the Protocol requirements (dementia, neurological or psychiatric disorders, drug or alcohol abuse, etc.); Simultaneous participation in any other clinical trial; participation in other clinical trials within 30 days before inclusion in the present study; previous participation in the present study. Acute infections or active chronic infections; Documented hepatitis B, active hepatitis C, HIV or syphilis infection; Intravenous administration of the drug is impossible; Intravenous administration of contrast agents is impossible; Hypersensitivity to any component of BCD-145. Known history of hypersensitivity to monoclonal antibodies; Pregnancy or breastfeeding;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 3+3 dose escalation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-145 Monotherapy Dose Level 1<br> | Biological: BCD-145<br>* Anti-CTLA-4 monoclonal antibody, IV infusion<br>|
| Experimental: BCD-145 Monotherapy Dose Level 2<br> | Biological: BCD-145<br>* Anti-CTLA-4 monoclonal antibody, IV infusion<br>|
| Experimental: BCD-145 Monotherapy Dose Level 3<br> | Biological: BCD-145<br>* Anti-CTLA-4 monoclonal antibody, IV infusion<br>|
| Experimental: BCD-145 Monotherapy Dose Level 4<br> | Biological: BCD-145<br>* Anti-CTLA-4 monoclonal antibody, IV infusion<br>|
| Experimental: BCD-145 Monotherapy Dose Level 5<br> | Biological: BCD-145<br>* Anti-CTLA-4 monoclonal antibody, IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Dose-Limiting Toxicities (DLTs) | The Investigators defined Dose-Limiting Toxicities (DLTs) as any treatment-related adverse events of grade 3 or greater, grade 3 or greater immune-mediated toxic effects (defined as an inflammatory process that compromised the function of any organ and was not attributable to another cause) that had the potential to be life threatening with continuation of therapy, immune-mediated toxic effects that did not resolve or improved to grade 2 or less within 14 days of onset | 85 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-Drug Antibody levels of BCD-145 | Binding and neutralizing anti-drug antibody levels of BCD-145 | 85 days | 
| Number of Participants With Objective Response | Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. Pilot efficacy assessment is not the primary objective of this study and will be conducted by surrogate endpoints describing the direct antitumor effect of the drug. | 85 days |