A Study to Compare Pharmacokinetics, Efficacy, Safety, and Immunogenicity of MB12 (Proposed Pembrolizumab Biosimilar) to Keytruda® in Non-small Cell Lung Cancer (BENITO Study)

Official title

Randomized, Multicenter, Multinational, Double-Blind Study to Compare the Pharmacokinetics, Efficacy, Safety and Immunogenicity of MB12 (Proposed Pembrolizumab Biosimilar) Versus Keytruda® in Combination With Chemotherapy for the Treatment of Patients With Advanced Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (BENITO Study)

Overview

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.

Interventions

• Drug MB12 (Proposed Pembrolizumab Biosimilar)
  200mg IV, every 3 weeks on Day 1
• Drug EU-sourced Keytruda®
  200mg IV, every 3 weeks on Day 1
• Drug US-sourced Keytruda®
  200mg IV, every 3 weeks on Day 1
• Drug Pemetrexed
  500 mg/m2 IV, every 3 weeks on Day 1
• Drug Carboplatin
  Area under the curve (AUC) 5 IV, every 3 weeks on Day 1 for 4 cycles.
• Drug Cisplatin
  75 mg/m2 IV, every 3 weeks on Day 1 for 4 cycles

Primary outcome measures

• To demonstrate the pharmacokinetic (PK) bioequivalence of MB12, EU-sourced Keytruda® and US-sourced Keytruda® in combination with chemotherapy [Time frame: Week 1 - Week 24]
• 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). [Time frame: Week 1 - Week 24]

Secondary outcome measures (4)

• To assess the efficacy of MB12 as compared with Keytruda® based on other efficacy parameters and timepoints over the study period. [Time frame: Week 1 - Week 52]
• 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. [Time frame: Week 1 - Week 52]
• To assess the safety and tolerability of MB12 as compared with Keytruda® [Time frame: Week 1 - Week 52]
• To assess the immunogenicity of MB12 as compared with Keytruda® [Time frame: Week 1 - Week 52]

Eligibility criteria

Inclusion criteria

• 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.
• Performance based on the Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Adequate hepatic, renal, hematologic, endocrine, and coagulation function.

Exclusion criteria

• 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.
• Active autoimmune disease that has required systemic treatment in the last 2 years.
• Contraindication and/or intolerance to the administration of pembrolizumab or known sensitivity to any component of pembrolizumab.
• Has a known sensitivity to any component of cisplatin, carboplatin, or pemetrexed.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Turkey (Türkiye) · 18 centers

Center list to be confirmed — check the primary protocol.

Spain · 16 centers

Center list to be confirmed — check the primary protocol.

Georgia · 12 centers

• Site 108004 — Batumi
• Site 108005 — Kutaisi
• Site 108011 — Marneuli
• Site 108001 — Tbilisi
• Site 108002 — Tbilisi
• Site 108003 — Tbilisi
• Site 108006 — Tbilisi
• Site 108007 — Tbilisi
• … and 4 more centers

Italy · 10 centers

• Site 113012 — Brescia
• Site 113010 — Cremona
• Site 113007 — Genova
• Site 113011 — Lecce
• Site 113009 — Meldola
• Site 113001 — Pavia
• Site 113003 — Roma
• Site 113006 — Roma
• … and 2 more centers

Greece · 9 centers

• Site 110006 — Athens
• Site 110003 — Kifissia
• Site 110004 — Larissa
• Site 110009 — Pátrai
• Site 110001 — Thessaloniki
• Site 110002 — Thessaloniki
• Site 110005 — Thessaloniki
• Site 110008 — Thessaloniki
• … and 1 more center

Taiwan · 8 centers

Center list to be confirmed — check the primary protocol.

Jordan · 7 centers

• Site 114001 — Amman
• Site 114002 — Amman
• Site 114003 — Amman
• Site 114004 — Amman
• Site 114005 — Amman
• Site 114007 — Amman
• Site 114006 — Irbid

Philippines · 7 centers

• Site 203006 — Bacolod City
• Site 203003 — Baguio City
• Site 203004 — Iloilo City
• Site 203009 — Iloilo City
• Site 203005 — Makati City
• Site 203007 — Manila
• Site 203002 — Quezon City

South Africa · 7 centers

Center list to be confirmed — check the primary protocol.

Thailand · 7 centers

Center list to be confirmed — check the primary protocol.

South Korea · 6 centers

Center list to be confirmed — check the primary protocol.

Poland · 5 centers

• Site 118004 — Katowice
• Site 118001 — Lodz
• Site 118005 — Lublin
• Site 118002 — Prabuty
• Site 118003 — Słupsk

Romania · 5 centers

• Site 120001 — Cluj-Napoca
• Site 120003 — Craiova
• Site 120004 — Craiova
• Site 120006 — Floreşti
• Site 120005 — Timișoara

Serbia · 5 centers

• Site 121001 — Belgrade
• Site 121002 — Belgrade
• Site 121004 — Kamenitz
• Site 121003 — Kragujevac
• … and 1 more center

Tunisia · 5 centers

Center list to be confirmed — check the primary protocol.

Armenia · 4 centers

• Site 101001 — Yerevan
• Site 101002 — Yerevan
• Site 101003 — Yerevan
• Site 101004 — Yerevan

Japan · 4 centers

• Site 207002 — Hakodate-shi
• Site 207012 — Okayama
• Site 207010 — Shinagawa-Ku
• Site 207001 — Shizuoka

Bosnia and Herzegovina · 3 centers

• Site 103001 — Sarajevo
• Site 103002 — Tuzla
• Site 103003 — Zenica

Malaysia · 3 centers

• Site 202001 — Cheras
• Site 202002 — Kota Bharu
• Site 202003 — Kuala Selangor

Panama · 3 centers

• Site 304001 — Panama City
• Site 304002 — Panama City
• Site 304003 — Panama City

Portugal · 3 centers

• Site 119001 — Lisbon
• Site 119002 — Matosinhos Municipality
• Site 119003 — Porto

Slovakia · 3 centers

Center list to be confirmed — check the primary protocol.

Moldova · 1 center

• Research site 116001 — Chisinau

Identifiers

NCT: NCT06687369 · MB12-C-02-24

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗