Phase I Study of BCD-145 (Anti-CTLA-4) in Patients With Unresectable/Metastatic Melanoma

A Multicenter Open-Label Single-Arm Multi-Cohort Phase I Study of Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of BCD-145 (JSC BIOCAD, Russia) in Patients With Unresectable/Metastatic Melanoma

A Multicenter Open-Label Single-Arm Multi-Cohort Phase I Study of Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of BCD-145 (JSC BIOCAD, Russia) Monotherapy in Patients with Unresectable/Metastatic Melanoma.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Biological: BCD-145

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • N.N. Blokhin National Medical Research Center of Oncology
  • Saint Petersburg, Russian Federation, 190013
    • JSC "Modern Medical Technologies"
  • Saint Petersburg, Russian Federation, 197758
    • N.N. Petrov National Medical Research Center of Oncology
  • Saint Petersburg, Russian Federation, 197758
    • Saint-Petersburg Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 (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);
4. ECOG score of 0 to 2;
5. Measurable disease (at least one lesion) according to RECIST v1.1 ;
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 16 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-145.

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 ;
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. Endocrine disorders: abnormal thyroid hormones
10. Prior anticancer treatment within 28 days before starting the study drug (surgery, radiation therapy , or chemotherapy);
11. Known history of more than 6 lines of systemic anticancer chemotherapy (including neoadjuvant and adjuvant CTs);
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 30 days before inclusion in the present study; previous participation in the present study.
16. Acute infections or active chronic infections;
17. Documented hepatitis B, active hepatitis C, HIV or syphilis infection;
18. Intravenous administration of the drug is impossible;
19. Intravenous administration of contrast agents is impossible;
20. Hypersensitivity to any component of BCD-145.
21. Known history of hypersensitivity to monoclonal antibodies;
22. Pregnancy or breastfeeding;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCD-145 Monotherapy Dose Level 1	Biological: BCD-145; Anti-CTLA-4 monoclonal antibody, IV infusion
Experimental: BCD-145 Monotherapy Dose Level 2	Biological: BCD-145; Anti-CTLA-4 monoclonal antibody, IV infusion
Experimental: BCD-145 Monotherapy Dose Level 3	Biological: BCD-145; Anti-CTLA-4 monoclonal antibody, IV infusion
Experimental: BCD-145 Monotherapy Dose Level 4	Biological: BCD-145; Anti-CTLA-4 monoclonal antibody, IV infusion
Experimental: BCD-145 Monotherapy Dose Level 5	Biological: BCD-145; Anti-CTLA-4 monoclonal antibody, IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Dose-Limiting Toxicities (DLTs)	The Investigators defined Dose-Limiting Toxicities (DLTs) as; any treatment-related adverse events of grade 3 or greater,; grade 3 or greater immune-mediated toxic effects (defined as an inflammatory process that compromised the function of any organ and was not attributable to another cause) that had the potential to be life threatening with continuation of therapy,; immune-mediated toxic effects that did not resolve or improved to grade 2 or less within 14 days of onset	85 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-Drug Antibody levels of BCD-145	Binding and neutralizing anti-drug antibody levels of BCD-145	85 days
Number of Participants With Objective Response	Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. 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.	85 days

Collaborators and Investigators

• Sponsor: Biocad
• Investigators: Study Director: Roman A Ivanov, PhD, Vice President R&D, JSC BIOCAD

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2017
• Primary Completion (Actual): September 11, 2018
• Study Completion (Actual): December 4, 2018

Study Registration Dates

• First Submitted: March 9, 2018
• First Submitted That Met QC Criteria: March 14, 2018
• First Posted (Actual): March 21, 2018

Study Record Updates

• Last Update Posted (Actual): May 9, 2019
• Last Update Submitted That Met QC Criteria: May 8, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: BCD-145-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No