phase i study of bcd-145 (anti-ctla-4) in patients with unresectable/metastatic melanoma

Conditions: Melanoma

Summary: 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.


Eligibility criteria:
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;