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

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

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.

Inclusion Criteria:

1. Patient provides a written informed consent and is able to follow the requirements of the Protocol;
2. Age ≥ 18 years
3. 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);
4. ECOG score of 0 to 2;
5. Measurable disease (at least one lesion) according to RECIST v1.1 ;
6. 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);
7. No severe pathology of organs or systems;
8. Life expectancy of at least 16 weeks from the screening;
9. 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:

1. Severe concomitant illnesses or life-threatening consequences (including pleural/pericardial/peritoneal effusion that requires medical intervention , pulmonary lymphangitis, or involvement of >50% renal parenchyma);
2. Brain metastases ;
3. Severe cardiovascular disorders within 6 months before screening;
4. Autoimmune diseases;
5. Conditions requiring steroids or any other immunosuppressants;
6. Blood disorders: ANC ≤1,500/mm3; platelets ≤100,000/mm3; or Hb ≤90 g/L;
7. Renal function impairment: creatinine ≥1.5 × ULN;
8. Hepatic function impairment: bilirubin ≥1.5 × ULN; AST and ALT ≥2.5 × ULN (5 × ULN for patients with liver metastases), AlkPh ≥ 5 × ULN;
9. Endocrine disorders: abnormal thyroid hormones
10. Prior anticancer treatment within 28 days before starting the study drug (surgery, radiation therapy , or chemotherapy);
11. Known history of more than 6 lines of systemic anticancer chemotherapy (including neoadjuvant and adjuvant CTs);
12. Prior treatment with anti-PD1/PDL1 agents or CTLA4 inhibitors;
13. Concurrent malignancy except for radically resected cervical carcinoma in situ or radically resected basal cell/squamous cell carcinoma;
14. Conditions limiting patient's ability to follow the Protocol requirements (dementia, neurological or psychiatric disorders, drug or alcohol abuse, etc.);
15. 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.
16. Acute infections or active chronic infections;
17. Documented hepatitis B, active hepatitis C, HIV or syphilis infection;
18. Intravenous administration of the drug is impossible;
19. Intravenous administration of contrast agents is impossible;
20. Hypersensitivity to any component of BCD-145.
21. Known history of hypersensitivity to monoclonal antibodies;
22. Pregnancy or breastfeeding;