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

NCT05668650 | Recruiting Phase 3 DMC

• 1 other identifier: MB12-C-01-22
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

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.

Conditions

Non Small Cell Lung Cancer Metastatic

Outcome Measures

Primary Outcomes (3)

• AUC (area under the curve)

  The primary PK parameter is AUC (area under the curve in the serum concentration-time plot) at Cycle 6. Serum concentrations used for estimating AUC will be determined by a validated analytical procedure once steady state (5 elimination half-lives) has been reached.

  Four months

• Cmax (maximum serum concentration)

  Cmax will be calculated for Cycle 1 and Cycle 6.

  Four months

• Tmax (time for maximum serum concentration)

  Tmax will be calculated for Cycle 1 and Cycle 6.

  Four months

Secondary Outcomes (3)

• Best overall response

  52 weeks

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  52 weeks

• Number of participants developing anti-drug antibodies

  52 weeks

Study Arms (2)

Medical Reference Product

ACTIVE COMPARATOR

Keytruda® will be administered as monotherapy, on Day 1 of every 3-week cycle (21 days), during the Main Study Period (6 cycles) unless there is disease progression, intolerance to the study drug, or treatment discontinuation for other reason, whichever occurs first. Those subjects with clinical benefit from treatment (CR, PR, and SD) as per the investigator's discretion, will be allowed to continue receiving treatment with MB12/Keytruda® in the Extended Study Period, according to the arm initially assigned, every 3 weeks, for a maximum of 52 weeks from the first infusion or until evidence of disease progression, intolerance to the study drug, or treatment discontinuation for other reason, whichever occurs first.

Drug: Pembrolizumab

Investigational Product

EXPERIMENTAL

MB12 will be administered as monotherapy, on Day 1 of every 3-week cycle (21 days), during the Main Study Period (6 cycles) unless there is disease progression, intolerance to the study drug, or treatment discontinuation for other reason, whichever occurs first. Those subjects with clinical benefit from treatment (CR, PR, and SD) as per the investigator's discretion, will be allowed to continue receiving treatment with MB12/Keytruda® in the Extended Study Period, according to the arm initially assigned, every 3 weeks, for a maximum of 52 weeks from the first infusion or until evidence of disease progression, intolerance to the study drug, or treatment discontinuation for other reason, whichever occurs first.

Drug: Pembrolizumab biosimilar

Interventions

Pembrolizumab DRUG

Study drug administration: intravenous infusion Dosing instructions: 200 mg administered over 30 minutes, every 3 weeks The time for infusion should be closer to 30 minutes. However, considering the variability of the infusion pumps from one center to another, a -5 to +10 minutes window is allowed (ie, the time for infusion is 30 minutes with an allowed range of 25 to 40 minutes).

Also known as: Keytruda

Medical Reference Product

Pembrolizumab biosimilar DRUG

Study drug administration: intravenous infusion Dosing instructions: 200 mg administered over 30 minutes, every 3 weeks The time for infusion should be closer to 30 minutes. However, considering the variability of the infusion pumps from one center to another, a -5 to +10 minutes window is allowed (ie, the time for infusion is 30 minutes with an allowed range of 25 to 40 minutes).

Also known as: MB12

Investigational Product

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals must meet all of the following criteria to be included in the study:
• Willing and able to provide written informed consent for the study before the initiation of any study-specific procedures.
• Greater than or equal to 18 years of age at the time of signing the ICF.
• Body weight ≥50 kg at Screening.
• Having newly diagnosed stage IV (defined by the eighth edition of the TNM classification) non-squamous NSCLC, without prior systemic treatment for the disease. For those subjects 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 per RECIST version 1.1, locally assessed.
• Programmed death-ligand 1 (PD-L1) expression ≥50%, locally determined by immunohistochemistry, as determined by a Food and Drug Administration (FDA) validated method.
• Life expectancy of at least 3 months.
• ECOG performance status of 0 to 1.
• Adequate hepatic, renal, hematologic, endocrine, and coagulation function, defined as:
• Liver function: bilirubin level ≤1.5 × the upper limit of normal (ULN) (≤3 × ULN for subjects with Gilbert's syndrome), albumin level ≥ lower limit of normal (LLN), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5 × ULN in subjects without liver metastases or ≤5 × ULN in subjects with liver metastases.
• Renal function: serum creatinine level ≤1.5 × ULN, calculated creatinine clearance ≥50 mL/min (Cockcroft-Gault formula).
• Hematologic function: absolute neutrophil count ≥1.5 × 109/L; platelet count ≥100 × 109/L, hemoglobin ≥9 g/dL.
• Endocrine function: thyroid stimulating hormone (TSH) within normal limits. If TSH is not within normal limits, the subject may still be eligible if T3 and free T4 are within normal limits.
• Coagulation: international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless subject is receiving anticoagulant therapy. Subjects on anticoagulant therapy must be on a stable anticoagulation regimen and have an INR not above the target therapeutic range for the 14 days before the first dose of the study drug.

You may not qualify if:

• Unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions.
• Predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the subject is ineligible.
• Participation in another clinical trial or treatment with another investigational agent within 4 weeks or 5 half-lives before randomization, whichever is longer.
• Known actionable mutations for which there is an approved and available therapy.
• Known central nervous system metastases and/or carcinomatous meningitis.
• Previous systemic steroid therapy (prednisone at a dose of 10 mg or equivalent) within 3 days before the first dose of the study drug or receiving any other form of immunosuppressive medication. Subjects receiving daily steroid replacement therapy (daily prednisone at a dose of 5 to 7.5 mg or equivalent) could be included in the study.
• Subject who requires any other form of localized or systemic antineoplastic therapy during the study.
• Prior anti-programmed cell death-1 (anti-PD-1), anti-PD-L1, anti programmed death-ligand 2 (anti-PD-L2), anti-CD137, or anti cytotoxic T lymphocyte antigen (CTLA)-4 therapy (including ipilimumab or any other antibody or drug that specifically targets co stimulation of T cells or immune checkpoints).
• Prior systemic cytotoxic chemotherapy, biological therapy, or major surgery within 3 weeks before the first dose of the study drug; have received thoracic radiation therapy of \>30 gray (Gy) within 6 months before the first dose of the study drug. Palliative radiotherapy is allowed if completed \>14 days before the first dose of the study drug.
• Known history of severe hypersensitivity to another monoclonal antibody.
• Active autoimmune disease which has required systemic treatment in the last 2 years before the first dose of the study drug (eg, disease modifying agents, corticosteroids, or immunosuppressive treatment). Replacement therapy (eg, thyroxine, insulin, or physiological corticosteroid replacement therapy for pituitary or adrenal insufficiency) is not considered a form of systemic treatment.
• Interstitial lung disease or pneumonitis requiring oral or intravenous steroids.
• Active infection or a previous infection requiring intravenous systemic treatment within 30 days before the first dose of the study drug.
• Subject who has received or is about to receive a live virus vaccination within 30 days before the first dose of the study drug. Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.
• Known history of human immunodeficiency virus (HIV)-1 or HIV-2.

Sponsors & Collaborators

• Laboratorio Elea Phoenix S.A.: lead
• Syneos Health: collaborator

Study Sites (1)

Clínica Viedma

Viedma, Río Negro Province, 5300, Argentina

RECRUITING

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Eduardo Spitzer, MSc

  Laboratorio Elea Phoenix

  STUDY CHAIR

Central Study Contacts

Marcelo Guthmann, PhD

CONTACT

+541144898300; marcelo.guthmann@elea.com

Marcelo Tinelli, MD

CONTACT

marcelo.tinelli@elea.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study will be double-blind during the whole study period. The double-blind design reduces the potential for bias, particularly in the assessment of AEs. Most of the other assessments in the current study are objective in nature and, therefore, less prone to bias. The blinding for a specific subject can be broken by the investigator (emergency code breaking) only if the investigator considers the information indispensable to the safety of the subject. All subjects whose treatment are unblinded by the investigator (break blind option, emergency code breaking) while on the study will be withdrawn at the moment of unblinding, with the reason for unblinding given as the reason for discontinuation from the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomized, multicenter, multinational, double-blind, and parallel-group study.

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: December 30, 2022
• Study Start: August 15, 2023
• Primary Completion: August 1, 2024
• Study Completion: December 1, 2024
• Last Updated: July 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

AR (1)