Clinical trial NCT06847334: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Non-Squamous Non-Small Cell Lung Cancer
Keywords: Keytruda biosimilar
Lead sponsor: Shanghai Henlius Biotech
Sponsor class: INDUSTRY
First posted: 2025-02-26
Enrollment: 772
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Primary outcomes:
measure: Area under the serum concentration-time curve from time 0 to 21 days (AUC0-21d)
timeFrame: Up to Day 21
measure: Area under the serum concentration-time curve within a dosing interval at steady state (AUCss)
timeFrame: Up to 1 year
measure: Best Objective Response Rate (BORR) assessed by Independent Radiology Review Committee (IRRC) based on RECIST v1.1
timeFrame: up to week 24
Secondary outcomes:
measure: Maximum serum drug concentration (Cmax) after the first dose
timeFrame: Up to Day 21
measure: Trough serum drug concentration (Ctrough) after the first dose
timeFrame: Up to Day 21
measure: Area under the serum concentration-time curve from time 0 to infinity (AUC0-inf) after the first dose
timeFrame: Up to Day 21
measure: Area under the serum concentration-time curve extrapolated from time t to infinity as a percentage of total AUC (%AUCex) after the first dose
timeFrame: Up to Day 21
measure: Time to reach maximum serum drug concentration (Tmax) after the first dose
timeFrame: Up to Day 21
measure: Elimination half life (t1/2) after the first dose
timeFrame: Up to Day 21
measure: Volume of distribution during terminal phase (Vz) after the first dose
timeFrame: Up to Day 21
measure: Total clearance (CL) after the first dose
timeFrame: Up to Day 21
measure: Mean residence time (MRT) after the first dose
timeFrame: Up to Day 21
measure: Maximum serum drug concentration at steady-state (Cmax, ss)
timeFrame: Up to 1 year
measure: Trough serum drug concentration at steady-state (Ctrough, ss)
timeFrame: Up to 1 year
measure: Average serum drug concentration at steady-state (Cave, ss)
timeFrame: Up to 1 year
measure: Time to reach maximum serum drug concentration at steady-state (Tmax, ss)
timeFrame: Up to 1 year
measure: Elimination half life at steady-state (t1/2, ss)
timeFrame: Up to 1 year
measure: Volume of distribution at steady-state (Vss)
timeFrame: Up to 1 year
measure: Total clearance at steady-state (CLss)
timeFrame: Up to 1 year
measure: Accumulation ratio of AUC (Rac(AUC))
timeFrame: Up to 1 year
measure: Accumulation ratio of Cmax (Rac(Cmax))
timeFrame: Up to 1 year
measure: Objective response rate (ORR) assessed by IRRC (based on RECIST v1.1)
timeFrame: Up to Week 24
measure: Objective response rate (ORR) assessed by Investigator (based on RECIST v1.1)
timeFrame: Up to Week 48
measure: Duration of response (DOR) assessed by the investigator (based on RECIST v1.1)
timeFrame: Up to Week 48
measure: Time to response (TTR) assessed by the investigator (based on RECIST v1.1)
timeFrame: Up to Week 48
measure: Progression free survival (PFS) assessed by the investigator (based on RECIST v1.1)
timeFrame: Up to Week 48
measure: Progression free survival rate (PFSR) assessed by the investigator (based on RECIST v1.1)
timeFrame: Up to Week 48
measure: Overall survival (OS)
timeFrame: Up to 1 year
measure: Overall survival rate (OSR)
timeFrame: Up to 1 year
measure: Adverse events (AEs)
timeFrame: Up to Month 15
measure: Serious adverse events (SAEs)
timeFrame: Up to Month 15
measure: Incidence of anti-drug antibodies (ADAs).
timeFrame: Up to 1 year
measure: Incidence of neutralizing antibodies (NAbs).
timeFrame: Up to 1 year
Other outcomes:
Locations:
Study officials:
References: