Phase I Study of BCD-145 (Anti-CTLA-4) in Patients With Unresectable/Metastatic Melanoma
Primary Purpose
Melanoma
Status
Completed
Phase
Phase 1
Locations
Russian Federation
Study Type
Interventional
Intervention
BCD-145
Sponsored by

About this trial
This is an interventional treatment trial for Melanoma
Eligibility Criteria
Inclusion Criteria:
- Patient provides a written informed consent and is able to follow the requirements of the Protocol;
- Age ≥ 18 years
- 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);
- ECOG score of 0 to 2;
- Measurable disease (at least one lesion) according to RECIST v1.1 ;
- 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);
- No severe pathology of organs or systems;
- Life expectancy of at least 16 weeks from the screening;
- 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:
- Severe concomitant illnesses or life-threatening consequences (including pleural/pericardial/peritoneal effusion that requires medical intervention , pulmonary lymphangitis, or involvement of >50% renal parenchyma);
- Brain metastases ;
- Severe cardiovascular disorders within 6 months before screening;
- Autoimmune diseases;
- Conditions requiring steroids or any other immunosuppressants;
- Blood disorders: ANC ≤1,500/mm3; platelets ≤100,000/mm3; or Hb ≤90 g/L;
- Renal function impairment: creatinine ≥1.5 × ULN;
- Hepatic function impairment: bilirubin ≥1.5 × ULN; AST and ALT ≥2.5 × ULN (5 × ULN for patients with liver metastases), AlkPh ≥ 5 × ULN;
- Endocrine disorders: abnormal thyroid hormones
- Prior anticancer treatment within 28 days before starting the study drug (surgery, radiation therapy , or chemotherapy);
- Known history of more than 6 lines of systemic anticancer chemotherapy (including neoadjuvant and adjuvant CTs);
- Prior treatment with anti-PD1/PDL1 agents or CTLA4 inhibitors;
- Concurrent malignancy except for radically resected cervical carcinoma in situ or radically resected basal cell/squamous cell carcinoma;
- Conditions limiting patient's ability to follow the Protocol requirements (dementia, neurological or psychiatric disorders, drug or alcohol abuse, etc.);
- 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.
- Acute infections or active chronic infections;
- Documented hepatitis B, active hepatitis C, HIV or syphilis infection;
- Intravenous administration of the drug is impossible;
- Intravenous administration of contrast agents is impossible;
- Hypersensitivity to any component of BCD-145.
- Known history of hypersensitivity to monoclonal antibodies;
- Pregnancy or breastfeeding;
Sites / Locations
- N.N. Blokhin National Medical Research Center of Oncology
- JSC "Modern Medical Technologies"
- N.N. Petrov National Medical Research Center of Oncology
- Saint-Petersburg Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
BCD-145 Monotherapy Dose Level 1
BCD-145 Monotherapy Dose Level 2
BCD-145 Monotherapy Dose Level 3
BCD-145 Monotherapy Dose Level 4
BCD-145 Monotherapy Dose Level 5
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Anti-Drug Antibody levels of BCD-145
Binding and neutralizing anti-drug antibody levels of BCD-145
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03472027
Brief Title
Phase I Study of BCD-145 (Anti-CTLA-4) in Patients With Unresectable/Metastatic Melanoma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
October 2, 2017 (Actual)
Primary Completion Date
September 11, 2018 (Actual)
Study Completion Date
December 4, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biocad
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
3+3 dose escalation
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BCD-145 Monotherapy Dose Level 1
Arm Type
Experimental
Arm Title
BCD-145 Monotherapy Dose Level 2
Arm Type
Experimental
Arm Title
BCD-145 Monotherapy Dose Level 3
Arm Type
Experimental
Arm Title
BCD-145 Monotherapy Dose Level 4
Arm Type
Experimental
Arm Title
BCD-145 Monotherapy Dose Level 5
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
BCD-145
Intervention Description
Anti-CTLA-4 monoclonal antibody, IV infusion
Primary Outcome Measure Information:
Title
Number of participants with Dose-Limiting Toxicities (DLTs)
Description
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
Time Frame
85 days
Secondary Outcome Measure Information:
Title
Anti-Drug Antibody levels of BCD-145
Description
Binding and neutralizing anti-drug antibody levels of BCD-145
Time Frame
85 days
Title
Number of Participants With Objective Response
Description
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.
Time Frame
85 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient provides a written informed consent and is able to follow the requirements of the Protocol;
Age ≥ 18 years
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);
ECOG score of 0 to 2;
Measurable disease (at least one lesion) according to RECIST v1.1 ;
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);
No severe pathology of organs or systems;
Life expectancy of at least 16 weeks from the screening;
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:
Severe concomitant illnesses or life-threatening consequences (including pleural/pericardial/peritoneal effusion that requires medical intervention , pulmonary lymphangitis, or involvement of >50% renal parenchyma);
Brain metastases ;
Severe cardiovascular disorders within 6 months before screening;
Autoimmune diseases;
Conditions requiring steroids or any other immunosuppressants;
Blood disorders: ANC ≤1,500/mm3; platelets ≤100,000/mm3; or Hb ≤90 g/L;
Renal function impairment: creatinine ≥1.5 × ULN;
Hepatic function impairment: bilirubin ≥1.5 × ULN; AST and ALT ≥2.5 × ULN (5 × ULN for patients with liver metastases), AlkPh ≥ 5 × ULN;
Endocrine disorders: abnormal thyroid hormones
Prior anticancer treatment within 28 days before starting the study drug (surgery, radiation therapy , or chemotherapy);
Known history of more than 6 lines of systemic anticancer chemotherapy (including neoadjuvant and adjuvant CTs);
Prior treatment with anti-PD1/PDL1 agents or CTLA4 inhibitors;
Concurrent malignancy except for radically resected cervical carcinoma in situ or radically resected basal cell/squamous cell carcinoma;
Conditions limiting patient's ability to follow the Protocol requirements (dementia, neurological or psychiatric disorders, drug or alcohol abuse, etc.);
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.
Acute infections or active chronic infections;
Documented hepatitis B, active hepatitis C, HIV or syphilis infection;
Intravenous administration of the drug is impossible;
Intravenous administration of contrast agents is impossible;
Hypersensitivity to any component of BCD-145.
Known history of hypersensitivity to monoclonal antibodies;
Pregnancy or breastfeeding;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roman A Ivanov, PhD
Organizational Affiliation
Vice President R&D, JSC BIOCAD
Official's Role
Study Director
Facility Information:
Facility Name
N.N. Blokhin National Medical Research Center of Oncology
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
JSC "Modern Medical Technologies"
City
Saint Petersburg
ZIP/Postal Code
190013
Country
Russian Federation
Facility Name
N.N. Petrov National Medical Research Center of Oncology
City
Saint Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
Facility Name
Saint-Petersburg Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)
City
Saint Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Phase I Study of BCD-145 (Anti-CTLA-4) in Patients With Unresectable/Metastatic Melanoma
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