This is a randomized, multicenter, multinational, double-blind, integrated pharmacokinetics (PK) and efficacy similarity study to compare the PK, efficacy, safety, and immunogenicity of MB12 versus Keytruda® in combination with pemetrexed-platinum chemotherapy as first-line treatment in patients with metastatic non-squamous NSCLC.
Adult male/female patients ≥18 years old at the time of signing the informed consent form (ICF).
Histologic or cytologic diagnosis of advanced NSCLC, stage IV (defined by the 8th edition of the Tumor Node Metastasis [TNM] classification), with no EGFR sensitizing (activating) mutation or ALK translocation, and who have not received prior systemic treatment for metastatic NSCLC. In those patients in whom the pleural or pericardial effusion is the only location of metastatic disease, confirmation of its malignant etiology is required.
At least 1 radiographically measurable lesion according to response evaluation criteria in solid tumors (RECIST) 1.1.
Known status of PD-L1 expression.
Predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the patient is not eligible.
Known history of central nervous system metastases and/or carcinomatous meningitis.
Prior anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte associated protein (CTLA)-4 therapy (including ipilimumab or any other antibody or drug that specifically targets co-stimulation of T-cells or immune checkpoints).
Major surgery within 3 weeks of the first dose of study treatment.
Parallel
MB12 (Proposed Pembrolizumab Biosimilar)
Drug200mg IV, every 3 weeks on Day 1
EU-sourced Keytruda®
Drug200mg IV, every 3 weeks on Day 1
US-sourced Keytruda®
Drug200mg IV, every 3 weeks on Day 1
Pemetrexed
Drug500 mg/m2 IV, every 3 weeks on Day 1
Carboplatin
DrugArea under the curve (AUC) 5 IV, every 3 weeks on Day 1 for 4 cycles.
Cisplatin
Drug75 mg/m2 IV, every 3 weeks on Day 1 for 4 cycles
To demonstrate the pharmacokinetic (PK) bioequivalence of MB12, EU-sourced Keytruda® and US-sourced Keytruda® in combination with chemotherapy
Area under the concentration-time curve (AUC) between Cycle 1 and Cycle 2 (AUC from time 0 to 504 hours postdose \[AUC0-504\]. AUC at steady state (AUCss) between Cycle 7 and Cycle 8.
To demonstrate the efficacy equivalence of MB12 and Keytruda® in combination with chemotherapy administered as first-line treatment in patients with advanced/metastatic non-squamous NSCLC (any PD-L1 expression type).
Objective response rate (ORR), up to and including 24 weeks (end of Cycle 8)
To assess the efficacy of MB12 as compared with Keytruda® based on other efficacy parameters and timepoints over the study period.
Objective response rate (ORR), Progression-free survival (PFS), Duration of response (DOR) and Overall survival (OS)
To compare the PK profile based on other PK parameters and timepoints (not covered by the primary PK endpoints) of MB12 as compared with Keytruda® over the study period.
Maximum concentration (Cmax), Time to maximum concentration (Tmax), Minimum concentration (Ctrough), Clearance (CL), Elimination half-life (t1/2), Distribution volume (Vd)
To assess the safety and tolerability of MB12 as compared with Keytruda®
Treatment-emergent adverse events (TEAEs)
To assess the immunogenicity of MB12 as compared with Keytruda®
Anti-drug antibodies (ADAs) and Neutralizing antibodies (NAbs) in ADA-positive samples
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