Non-Squamous Non-Small Cell Lung Cancer
Conditions
Keywords
Keytruda biosimilar
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).
Interventions
DRUGHLX17
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.
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.
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.
Sponsors
Shanghai Henlius Biotech
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| Area under the serum concentration-time curve from time 0 to infinity (AUC0-inf) 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 |
| Maximum serum drug concentration (Cmax) after the first dose | Up to Day 21 |
| 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 (OS) | Up to 1 year |
| Overall survival rate (OSR) | 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 |
| Accumulation ratio of AUC (Rac(AUC)) | Up to 1 year |
| Trough serum drug concentration (Ctrough) 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 |
Outcome results
None listed