a multicenter open-label single-arm multi-cohort phase i study of bcd-100 in patients with advanced solid tumors

Conditions: Melanoma; Lung Cancer; Renal Cell Carcinoma

Summary: 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


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 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); 4. ecog score of 0 to 2; 5. measurable disease (at least one lesion) according to recist v. 1.1 ; 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 12 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-100. 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, 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 ; 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. prior anticancer treatment within 28 days before starting the study drug (surgery, radiation therapy , or chemotherapy); 10. known history of more than 6 lines of systemic anticancer chemotherapy (including neoadjuvant and adjuvant cts); 11. prior treatment with anti-pd1/pdl1 agents or ctla4 inhibitors; 12. concurrent malignancy except for radically resected cervical carcinoma in situ or radically resected basal cell/squamous cell carcinoma; 13. conditions limiting patient's ability to follow the protocol requirements (dementia, neurological or psychiatric disorders, drug or alcohol abuse, etc.); 14. 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. 15. acute infections or active chronic infections; 16. documented hiv infection; 17. positive screening results for hbs-antigen, hepatitis b core antibodies (anti-hbc ab) and/or hepatitis c antibodies ; 18. positive results of microprecipitation reaction together with positive tpha assay results at the screening; 19. body weight \> 95 kg. 20. intravenous administration of the drug is impossible; 21. intravenous administration of contrast agents is impossible; 22. hypersensitivity to any component of bcd-100. 23. known history of hypersensitivity to monoclonal antibodies; 24. pregnancy or breastfeeding;