Double-blind Study to Evaluate the PK, Efficacy, Safety and Immunogenicity of MB12 Versus Keytruda® in Stage IV NSCLC

MB12 is being developed by mAbxience Research S.L., and its clinical development issponsored by Laboratorio Elea Phoenix S.A. as a proposed biosimilar to Keytruda┬«. Thereference medicinal product is European Union (EU)‐sourced Keytruda┬«, manufactured andmarketed by Merck Sharp & Dohme.Study drugs: MB12 and Keytruda┬« Study drug administration: intravenous infusion Dosinginstructions: 200 mg administered over 30 minutes, every 3 weeksThe 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 whodemonstrate clinical benefit from the treatment (CR, PR, and SD). They will continuetreatment until disease progression, intolerance to the study drug, treatmentdiscontinuation for other reason, or up to Week 52, whichever occurs first.The anti‐tumor activity will be determined by local radiological examination for allmeasurable and evaluable lesions according to RECIST version 1.1. During the Main StudyPeriod, 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 performedevery 9 weeks, from Week 18 onwards, according to RECIST criteria, until diseaseprogression, 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, thyroidfunction, coagulation, virology, urinalysis, and pregnancy tests), and AE assessments.The primary PK parameter is AUCss at Cycle 6. Serum concentrations used for estimatingAUCss will be determined by a validated analytical procedure once steady state (5elimination 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, asapplicable. Additional PK parameters may be included if deemed appropriate.PK variables will be calculated according to the recommendations of the EuropeanMedicines Agency (EMA) and the World Health Organization (WHO).Blood samples for PK analysis will be collected at Cycle 1 and Cycle 6 as follows:predose; at 30 minutes after the SOI; at 4, 6, 24, 48, 168, 336, and 504 hours after theSOI.The comparison of the immunogenicity profile of MB12 versus Keytruda┬« during the MainStudy and Extended Treatment Periods include: ‐ ADAs ‐ Nabs in ADA (+) samples ‐ Titers in ADA (+) samples During the Main Study Period, blood samples forimmunogenicity will be collected pre‐dose at Cycle 1 Day 1, Cycle 1 Day 14, pre‐doseat Cycle 3 Day 1, and pre‐dose at Cycle 6 Day 1. During the Extended TreatmentPeriod, 2 additional samples will be collected in those subjects who continuetreatment after Cycle 6 at Week 26 and at Week 52 or EOT/early termination (if thisoccurs before Week 52 and if previous sample has not been taken within the last 16weeks).