A Study of BCD-135 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, Safety, and Immunogenicity of BCD-135 (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, Safety, and Immunogenicity of BCD-135 (JSC BIOCAD, Russia) in Patients With Advanced Solid Tumors

Conditions
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Melanoma, NSCLC, Renal Cell Carcinoma, Bladder Cancer

Intervention / Treatment
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* Drug: BCD-135


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 or subsequent therapy lines); Locally advanced or metastatic EGFR/ALK wt NSCLC (squamous cell carcinoma/adenocarcinoma), progressive after the first-line therapy with platinum-based CT or EGFR/ALK wt NSCLC progressive after the first-line therapy with EGFR/ALK inhibitors (the drug will be used as a second therapy line); Metastatic clear cell renal carcinoma, progressive after at least the first-line therapy (the drug will be used as a second or third therapy lines); Locally advanced or metastatic bladder cancer progressive on/after therapy with platinum-based CT (the drug will be used as a second therapy line); ECOG score of 0 to 1; Presence of blocks for histological examination and/or patient's agreement to conduct a biopsy of an accessible lesions to obtain a histological material for examination of PD-L1 status Measurable disease (at least one lesion) according to RECISTv.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; LDH level >2 ULN; Prior anticancer treatment within 28 days before starting the study drug (surgery, radiation therapy, targeted therapy, immunotherapy, vaccine treatment or chemotherapy); More than 2 therapy lines of unresectable/metastatic melanoma, 1 therapy line of metastatic NSCLC, 2 therapy lines of metastatic RCC; 1 therapy line of metastatic BC; 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 28 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 > 100 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-135<br>Dose-escalation Arm (0.4, 1, 3, 10, 20 mg/kg) | Drug: BCD-135<br>* Monoclonal anti-PD-L1 antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DCR | Disease control rate (CR+PR+SD). 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 |