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

Phase 1

• Conditions: NSCLC; Renal Cell Carcinoma; Bladder Cancer; Melanoma
• Interventions: Drug: BCD-135

• Registration Number: NCT03464032
• Lead Sponsor: Biocad

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2017-10-31
• Status Verified: 2018-03
• Study First Submitted: 2018-03-07
• Study First Submitted QC: 2018-03-12
• Last Update Submitted: 2018-03-12
• Study First Posted: 2018-03-13
• Last Update Posted: 2018-03-13
• Primary Completion: 2018-05-31
• Study Completion: 2018-10-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BCD-135	BCD-135	Dose-escalation Arm (0.4, 1, 3, 10, 20 mg/kg)

Primary Outcome Measures

Name	Time	Method
DCR	85 days	Disease control rate (CR+PR+SD). Pilot efficacy assessment is not the primary objective of this study and will be conducted by surrogate endpoints describing the direct antitumor effect of the drug.

Trial Locations

Locations (1)

LLC BioEk; 🇷🇺 Saint-Petersburg, Russian Federation