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

Official title

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

Overview

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.

Detailed description

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).

Interventions

• Drug 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.
• Drug 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.
• Drug 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.

Primary outcome measures

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

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

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

Double blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06847334 · HLX17-NSCLC301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗