A Multicenter Open-Label Single-Arm Multi-Cohort Phase I Study of BCD-100 in Patients With Advanced Solid Tumors

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-100 (JSC BIOCAD, Russia) in Patients with Advanced Solid Tumors

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-100 (JSC BIOCAD, Russia) in Patients With Advanced Solid Tumors

Conditions
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Melanoma, Lung Cancer, Renal Cell Carcinoma

Intervention / Treatment
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* Biological: BCD-100


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 cancer (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); Locally advanced or metastatic NSCLC (squamous cell carcinoma/adenocarcinoma), progressive after at least the first-line therapy (the drug will be used as a second or subsequent therapy lines); Metastatic clear cell renal carcinoma, progressive after at least the first-line therapy (the drug will be used as a second or subsequent therapy lines); In addition, by investigator's decision, patients with the following malignancies can also be enrolled in the study : Pleural mesothelioma progressive after at least one therapy line (the drug will be used as a second or subsequent therapy lines); Metastatic bladder cancer progressive after at least one therapy line (the drug will be used as a second or subsequent therapy lines); Triple negative breast cancer (ER-, PR-, HER2-) progressive after at least the first-line therapy (the drug will be used as a second or subsequent therapy lines); ECOG score of 0 to 2; Measurable disease (at least one lesion) according to RECIST v. 1.1 ; 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 12 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-100. 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, progressive or associated with clinical symptoms (e.g. cerebral edema or spinal cord compression). Exclusions: metastases that do not progress and do not require steroids and/or anticonvulsants within at least 4 weeks before randomization ; 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; 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 HIV infection; Positive screening results for Hbs-antigen, hepatitis B core antibodies (anti-HBc Ab) and/or hepatitis C antibodies ; Positive results of microprecipitation reaction together with positive TPHA assay results at the screening; Body weight > 95 kg. Intravenous administration of the drug is impossible; Intravenous administration of contrast agents is impossible; Hypersensitivity to any component of BCD-100. 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-100 0.3 mg/kg<br>Patients who receive BCD-100 in a dose of 0.3 mg/kg | Biological: BCD-100<br>* Anti-PD1 monoclonal antibody<br>|
| Experimental: BCD-100 1 mg/kg<br>Patients who receive BCD-100 in a dose of 1 mg/kg | Biological: BCD-100<br>* Anti-PD1 monoclonal antibody<br>|
| Experimental: BCD-100 3 mg/kg<br>Patients who receive BCD-100 in a dose of 3 mg/kg | Biological: BCD-100<br>* Anti-PD1 monoclonal antibody<br>|
| Experimental: BCD-100 10 mg/kg<br>Patients who receive BCD-100 in a dose of 10 mg/kg | Biological: BCD-100<br>* Anti-PD1 monoclonal antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR (CR + PR) | 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. • ORR (CR + PR) after 85 days of therapy with BCD-100. | 85 days |