Double-blind Study to Evaluate the PK, Efficacy, Safety and Immunogenicity of MB12 Versus Keytruda® in Stage IV NSCLC
brief summary
This is a randomized, multicenter, multinational, double-blind, and parallel-group study to evaluate the PK, efficacy, safety and immunogenicity of MB12 (proposed pembrolizumab biosimilar) versus Keytruda® in subjects with newly diagnosed stage IV non-squamous NSCLC. This study is planned to be conducted in approximately 48 sites in 7 countries, a total of 174 subjects will be enrolled. Eligible subjects will be randomized in a 1:1 ratio to receive MB12 or Keytruda® at a dose of 200 mg every 3 weeks. Subjects will be stratified by gender (male versus female) and ECOG status (0 versus 1) as both factors are considered to have the potential to influence PK properties of pembrolizumab to some extent. The study will consist of 2 periods defined as follows: * Main Study Period from Screening up to Cycle 6 included. * Extended Treatment Period from Cycle 7 up to Week 52 for those subjects who demonstrate clinical benefit from the treatment (complete response \[CR\], partial response \[PR\], and stable disease \[SD\]). They will continue treatment until disease progression, intolerance to the study drug, treatment discontinuation for other reason, or up to Week 52, whichever occurs first. A Data Safety Monitoring Board (DSMB) will assess the safety data periodically and will recommend to the sponsor whether to continue, modify, or stop the trial on the basis of safety considerations. After the first 10 subjects have received at least 2 cycles of treatment, the DSMB will review the accumulated safety data, and the first meeting will take place. Subsequent meetings will be performed as per the DSMB charter.
detailed description
MB12 is being developed by mAbxience Research S.L., and its clinical development is sponsored by Laboratorio Elea Phoenix S.A. as a proposed biosimilar to Keytruda®. The reference medicinal product is European Union (EU)-sourced Keytruda®, manufactured and marketed by Merck Sharp \& Dohme.
Study drugs: MB12 and Keytruda® Study drug administration: intravenous infusion Dosing instructions: 200 mg administered over 30 minutes, every 3 weeks
The study will consist of 2 periods defined as follows:
* Main Study Period from Screening up to Cycle 6 included. * Extended Treatment Period from Cycle 7 up to Week 52 for those subjects who demonstrate clinical benefit from the treatment (CR, PR, and SD). They will continue treatment until disease progression, intolerance to the study drug, treatment discontinuation for other reason, or up to Week 52, whichever occurs first.
The anti-tumor activity will be determined by local radiological examination for all measurable and evaluable lesions according to RECIST version 1.1. During the Main Study Period, the efficacy assessments will be performed every 6 weeks from the first infusion (Cycle 1, Day 1). During the Extended Treatment Period, the assessments will be performed every 9 weeks, from Week 18 onwards, according to RECIST criteria, until disease progression, intolerance to the study drug, treatment discontinuation for other reason, or up to 52 weeks, whichever occurs first.
Safety assessments include vital signs, physical examination, ECOG performance status, 12-lead ECGs, clinical laboratory assessments (hematology, clinical chemistry, thyroid function, coagulation, virology, urinalysis, and pregnancy tests), and AE assessments.
The primary PK parameter is AUCss at Cycle 6. Serum concentrations used for estimating AUCss will be determined by a validated analytical procedure once steady state (5 elimination half-lives) has been reached.
Secondary PK parameters, including maximum concentration (Cmax), minimum concentration (Ctrough), time to maximum concentration (tmax), clearance (CL), elimination half-life (t1/2), and volume of distribution (Vss), will be calculated for Cycle 1 and Cycle 6, as applicable. Additional PK parameters may be included if deemed appropriate.
PK variables will be calculated according to the recommendations of the European Medicines Agency (EMA) and the World Health Organization (WHO).
official title
Randomized, Multicenter, Multinational, Double-blind Study to Evaluate the PK, Efficacy, Safety and Immunogenicity of MB12 (Proposed Pembrolizumab Biosimilar) Versus Keytruda® in Subjects With Stage IV NSCLC