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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Squamous Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: HLX17; Drug: US-sourced Keytruda®; Drug: EU-sourced Keytruda®

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).

• Study Type: Interventional
• Enrollment (Estimated): 772
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLX17 group; Recombinant anti-programmed death receptor-1- humanized antibody injection developed by Shanghai Henlius Biotech, Inc.	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.
Active Comparator: US-sourced Keytruda® group; US-sourced Keytruda	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.
Active Comparator: EU-sourced Keytruda® group; EU-sourced Keytruda	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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	Up to 1 year
Adverse events (AEs)	Up to Month 15
Serious adverse events (SAEs)	Up to Month 15
Incidence of anti-drug antibodies (ADAs).	Up to 1 year
Incidence of neutralizing antibodies (NAbs).	Up to 1 year
Maximum serum drug concentration (Cmax) after the first dose	Up to Day 21
Trough serum drug concentration (Ctrough) after the first dose	Up to Day 21
Area under the serum concentration-time curve from time 0 to infinity (AUC0-inf) after the first dose	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	Up to Day 21
Time to reach maximum serum drug concentration (Tmax) after the first dose	Up to Day 21
Elimination half life (t1/2) after the first dose	Up to Day 21
Volume of distribution during terminal phase (Vz) after the first dose	Up to Day 21
Total clearance (CL) after the first dose	Up to Day 21
Mean residence time (MRT) after the first dose	Up to Day 21
Maximum serum drug concentration at steady-state (Cmax, ss)	Up to 1 year
Trough serum drug concentration at steady-state (Ctrough, ss)	Up to 1 year
Average serum drug concentration at steady-state (Cave, ss)	Up to 1 year
Time to reach maximum serum drug concentration at steady-state (Tmax, ss)	Up to 1 year
Elimination half life at steady-state (t1/2, ss)	Up to 1 year
Volume of distribution at steady-state (Vss)	Up to 1 year
Total clearance at steady-state (CLss)	Up to 1 year
Accumulation ratio of AUC (Rac(AUC))	Up to 1 year
Accumulation ratio of Cmax (Rac(Cmax))	Up to 1 year
Objective response rate (ORR) assessed by IRRC (based on RECIST v1.1)	Up to Week 24
Objective response rate (ORR) assessed by Investigator (based on RECIST v1.1)	Up to Week 48
Duration of response (DOR) assessed by the investigator (based on RECIST v1.1)	Up to Week 48
Time to response (TTR) assessed by the investigator (based on RECIST v1.1)	Up to Week 48
Progression free survival (PFS) assessed by the investigator (based on RECIST v1.1)	Up to Week 48
Progression free survival rate (PFSR) assessed by the investigator (based on RECIST v1.1)	Up to Week 48
Overall survival rate (OSR)	Up to 1 year

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Estimated): April 27, 2025
• Primary Completion (Estimated): April 9, 2027
• Study Completion (Estimated): January 24, 2028

Study Registration Dates

• First Submitted: February 20, 2025
• First Submitted That Met QC Criteria: February 21, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Keytruda biosimilar
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: HLX17-NSCLC301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No