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

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 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);

4. ECOG score of 0 to 1;

5. 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

6. Measurable disease (at least one lesion) according to RECISTv.1.1;

7. 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);

8. No severe pathology of organs or systems;

9. Life expectancy of at least 12 weeks from the screening;

10. 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. LDH level >2 ULN;

10. Prior anticancer treatment within 28 days before starting the study drug (surgery, radiation therapy, targeted therapy, immunotherapy, vaccine treatment or chemotherapy);

11. 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;

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 28 days before inclusion in the present study; previous participation in the present study.

16. Acute infections or active chronic infections;

17. Documented HIV infection;

18. Positive screening results for Hbs-antigen, hepatitis B core antibodies (anti-HBc Ab) and/or hepatitis C antibodies;

19. Positive results of microprecipitation reaction together with positive TPHA assay results at the screening;

20. Body weight > 100 kg.

21. Intravenous administration of the drug is impossible;

22. Intravenous administration of contrast agents is impossible;

23. Hypersensitivity to any component of BCD-100.

24. Known history of hypersensitivity to monoclonal antibodies;

25. Pregnancy or breastfeeding;