Clinical Trial to Evaluate the PK and Safety of BCD-201 and Keytruda® in Patients With Advanced Malignancies

Study Overview
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Brief Summary
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Clinical study BCD-201-1 is a double-blind randomized study of the pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity of BCD-201 versus Keytruda following intravenous administration to subjects with advanced unresectable, metastatic, or recurrent melanoma and NSCLC. The study aimed to establish the equivalence of PK and similarity of the safety, immunogenicity, and PD profiles of BCD-201 and Keytruda.

Official Title
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A Multicenter, Double-Blind, Randomized Clinical Study to Evaluate the Pharmacokinetics and Safety of BCD-201 (JSC BIOCAD, Russia) and Keytruda® in Patients With Different Advanced Malignancies

Conditions
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Melanoma, Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: BCD-201
* Drug: Keytruda


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent; Body weight 60 to 90 kg; Histologically confirmed melanoma or NSCLC (patients with NSCLC are eligible to participate if high tumor PD-L1 expression [≥50%] is confirmed by local or central laboratory results); ECOG score 0-1; Laboratory test results consistent with adequate functioning of systems and organs; Willingness of males and females of childbearing potential to use highly effective contraceptive methods from the signing of the informed consent form, throughout the study and within 6 months after the administration of the last product dose Exclusion Criteria: Indications for radical therapy (surgery, radiation therapy); Previous systemic anti-tumor therapy for advanced unresectable, recurrent or metastatic melanoma or NSCLC (history of neoadjuvant or adjuvant therapy is acceptable provided that the treatment was completed at least 6 weeks prior to randomization); Active metastases in the central nervous system and/or carcinomatous meningitis; Patients with severe concomitant disorders, life-threatening acute complications of the primary disease (including massive pleural, pericardial, or peritoneal effusions requiring intervention, pulmonary lymphangitis, bleeding or organ perforation) at the time of signing the informed consent and during the screening period; For patients with NSCLC: presence of activating EGFR mutations/ALK translocations; Concomitant diseases and/or conditions that significantly increase the risk of AEs during the study; Active, known or suspected autoimmune disorders (subjects with type 1 diabetes mellitus or hypothyroidism requiring only hormone-replacement therapy and those with skin disorders [vitiligo, alopecia, or psoriasis] not requiring systemic therapy are eligible to participate); The need for therapy with glucocorticoids or any other drugs with immunosuppressive effects within 14 days prior to randomization; History of (non-infectious) pneumonitis requiring glucocorticoid therapy or pneumonitis at the time of screening; Hypersensitivity or allergy to any of the pembrolizumab product components; Pregnancy or breastfeeding, as well as intention to become pregnant or father a child during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>BCD-201 200 mg by intravenous infusions once every 3 weeks | Drug: BCD-201<br>* up to 8 treatment cycles<br>* Other names: pembrolizumab;|
| Active Comparator: Group 2<br>Keytruda 200 mg by intravenous infusions once every 3 weeks | Drug: Keytruda<br>* up to 8 treatment cycles<br>* Other names: pembrolizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-504) of pembrolizumab | area under the drug concentration-time curve in the time interval from 0 to 504 hours | pre-dose to week 25, 77 timepoints | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-∞) of pembrolizumab | Area under the drug concentration-time curve in the time interval from 0 to ∞ | pre-dose to week 25, 77 timepoints | 
| Cmax | maximum concentration of pembrolizumab | pre-dose to week 25, 77 timepoints | 
| Tmax | time to maximum concentration of pembrolizumab | pre-dose to week 25, 77 timepoints | 
| T½ | Half-life period | pre-dose to week 25, 77 timepoints | 
| Vd | Steady-state volume of distribution of the drug substance | pre-dose to week 25, 77 timepoints | 
| Cmin | minimum concentration of pembrolizumab | pre-dose to week 25, 77 timepoints | 
| kel | Elimination rate constant | pre-dose to week 25, 77 timepoints | 
| Cl | Total clearance | pre-dose to week 25, 77 timepoints | 
| Safety assessment | proportion of patients with any adverse events (AEs); • proportion of patients with severe AEs; proportion of patients who discontinued study therapy due to AEs; • proportion of patients with immune-mediated AEs | Day 1 to Day 169 | 
| Immunogenicity assessment | the frequency of binding and neutralizing anti-pembrolizumab antibody production | pre-dose to week 25, 5 timepoints | 
| To compare the results of pilot assessment of BCD-201 and Keytruda efficacy | overall response rate (ORR) | Day 1 to week 25 |