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
概览
- 阶段
- 3 期
- 干预措施
- Pembrolizumab
- 疾病 / 适应症
- Non Small Cell Lung Cancer Metastatic
- 发起方
- Laboratorio Elea Phoenix S.A.
- 入组人数
- 174
- 试验地点
- 1
- 主要终点
- Cmax (maximum serum concentration)
- 状态
- 招募中
- 最后更新
- 去年
概览
简要总结
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.
详细描述
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). 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 the SOI. The comparison of the immunogenicity profile of MB12 versus Keytruda® during the Main Study and Extended Treatment Periods include: * ADAs * Nabs in ADA (+) samples * Titers in ADA (+) samples During the Main Study Period, blood samples for immunogenicity will be collected pre-dose at Cycle 1 Day 1, Cycle 1 Day 14, pre-dose at Cycle 3 Day 1, and pre-dose at Cycle 6 Day 1. During the Extended Treatment Period, 2 additional samples will be collected in those subjects who continue treatment after Cycle 6 at Week 26 and at Week 52 or EOT/early termination (if this occurs before Week 52 and if previous sample has not been taken within the last 16 weeks).
研究者
入排标准
入选标准
- •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
- •Adequate hepatic, renal, hematologic, endocrine, and coagulation function, defined as:
排除标准
- •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.
研究组 & 干预措施
Medical Reference Product
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.
干预措施: Pembrolizumab
Investigational Product
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.
干预措施: Pembrolizumab biosimilar
结局指标
主要结局
Cmax (maximum serum concentration)
时间窗: Four months
Cmax will be calculated for Cycle 1 and Cycle 6.
AUC (area under the curve)
时间窗: Four months
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.
Tmax (time for maximum serum concentration)
时间窗: Four months
Tmax will be calculated for Cycle 1 and Cycle 6.
次要结局
- Number of participants developing anti-drug antibodies(52 weeks)
- Best overall response(52 weeks)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(52 weeks)