Brief Title: A Study of BCD-135 in Patients With Advanced Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

• Melanoma
• NSCLC
• Renal Cell Carcinoma
• Bladder Cancer

ELIGIBILITY

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;

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Svetlana Odintsova, MD

Role: Principal Investigator

Affiliation: LLC BioEk

Overall Contact

Name: Mariia Shustova, MD

Phone: +7 (812) 380 49 33

Email: shustova@biocad.ru

LOCATION