A Study to Compare the Efficacy, Safety, Immunogenicity, and Pharmacokinetic Profile of HLX17 Vs. Keytruda® in the First-Line Treatment of Advanced Non-squamous Non-small Cell Lung Cancer

Официальное название

A Multicentre, Randomized, Double-Blind, Parallel-Controlled Integrated Phase I/III Clinical Study to Evaluate the Efficacy, Safety and Pharmacokinetic Profile of HLX17 Vs. Keytruda® (US-sourced Keytruda® and EU-sourced Keytruda®) in the First-Line Treatment of Advanced Non-squamous Non-small Cell Lung Cancer

Обзор

This is a multicentre, randomized, double-blind, parallel-controlled integrated phase I/III clinical study to evaluate the similarity in efficacy, safety, PK profile, and immunogenicity of HLX17 vs. Keytruda®( US- and EU-sourced) in the first-line treatment of advanced non-squamous non-small cell lung cancer.

Подробное описание

This study includes three treatment groups. Patients will be randomly assigned at a 2:1:1 ratio to the HLX17, US-sourced Keytruda® and EU-sourced Keytruda® group to receive the treatment of IMPs in combination with Carboplatin Plus Pemetrexed until disease progression, initiation of new anti-tumor therapy, withdrawal of informed consent form, death, unacceptable toxicity, or up to 17 cycles (whichever occurs first).

Вмешательства

• Препарат HLX17
  HLX17 will be administered as IV infusion at a dose of 200mg on Day 1 of each 21-day cycle in combination with Carboplatin and Pemetrexed until loss of clinical benefit or up to 1 year.
• Препарат US-sourced Keytruda®
  US-sourced Keytruda® will be administered as IV infusion at a dose of 200mg on Day 1 of each 21-day cycle in combination with Carboplatin and Pemetrexed. After 24 weeks, all subjects in the US-Keytruda® group will receive HLX17 in combination with Pemetrexed until loss of clinical benefit or up to 1 year.
• Препарат EU-sourced Keytruda®
  EU-sourced Keytruda® will be administered as IV infusion at a dose of 200mg on Day 1 of each 21-day cycle in combination with Carboplatin and Pemetrexed until loss of clinical benefit or up to 1 year.

Первичные конечные точки

• Area under the serum concentration-time curve from time 0 to 21 days (AUC0-21d) [Срок оценки: Up to Day 21]
• Area under the serum concentration-time curve within a dosing interval at steady state (AUCss) [Срок оценки: Up to 1 year]
• Best Objective Response Rate (BORR) assessed by Independent Radiology Review Committee (IRRC) based on RECIST v1.1 [Срок оценки: up to week 24]

Вторичные конечные точки (12)

• Maximum serum drug concentration (Cmax) after the first dose [Срок оценки: Up to Day 21]
• Trough serum drug concentration (Ctrough) after the first dose [Срок оценки: Up to Day 21]
• Area under the serum concentration-time curve from time 0 to infinity (AUC0-inf) after the first dose [Срок оценки: Up to Day 21]
• Area under the serum concentration-time curve extrapolated from time t to infinity as a percentage of total AUC (%AUCex) after the first dose [Срок оценки: Up to Day 21]
• Time to reach maximum serum drug concentration (Tmax) after the first dose [Срок оценки: Up to Day 21]
• Elimination half life (t1/2) after the first dose [Срок оценки: Up to Day 21]
• Volume of distribution during terminal phase (Vz) after the first dose [Срок оценки: Up to Day 21]
• Total clearance (CL) after the first dose [Срок оценки: Up to Day 21]
• Mean residence time (MRT) after the first dose [Срок оценки: Up to Day 21]
• Maximum serum drug concentration at steady-state (Cmax, ss) [Срок оценки: Up to 1 year]
• Trough serum drug concentration at steady-state (Ctrough, ss) [Срок оценки: Up to 1 year]
• Average serum drug concentration at steady-state (Cave, ss) [Срок оценки: Up to 1 year]

Критерии участия

Критерии включения

• Histologically or cytologically confirmed diagnosis of stage IV inoperable to surgery or radiotherapy (AJCC 8th edition) non-squamous NSCLC.
• Without any tumor activating EGFR mutation or ALK or ROS1 gene rearrangement.
• Have not received prior systemic treatment for their advanced/metastatic NSCLC.
• At least one measurable lesion as assessed by IRRC based on RECIST v1.1.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
• Have adequate organ function.

Критерии исключения

• Subjects with NSCLC of other histopathological types, such as mixed adenosquamous carcinoma, and subjects with small cell lung cancer or neuroendocrine carcinoma.
• Subjects with other active malignancies within 5 years or at the same time prior to screening.
• Active central nervous system metastases.
• Known interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, and severe lung function abnormalities that may impede the investigators' diagnosis and management of drug-related pulmonary toxicity.
• Known active or suspected autoimmune diseases.
• History of immunodeficiency, including HIV antibody positive, active hepatitis B; or hepatitis C virus infections.
• Have received pembrolizumab or any other immune checkpoints inhibitors (PD-1, PD-L1, CTLA4, etc.) before screening.
• Pregnant or breastfeeding female.
• The investigator has a clear reason to believe that participation in this study would be detrimental to the subject.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06847334 · HLX17-NSCLC301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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