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

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

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

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;