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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: BCD-201; Drug: Keytruda

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • "Russian Cancer Research Center named after N.N. Blokhin "of the Ministry of Health of the Russian Federation
  • Omsk, Russian Federation
    • Budgetary healthcare institution of the Omsk region "Clinical oncological dispensary"
  • Saint Petersburg, Russian Federation, 197758
    • State Budgetary Healthcare Institution "Saint Petersburg Clinical Research and Practice Center for Specialized Medical Care (Oncology)"

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Biocad

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2021
• Primary Completion (Actual): June 21, 2022
• Study Completion (Estimated): August 31, 2023

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: February 13, 2023
• First Posted (Actual): February 22, 2023

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: BCD-201-1

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