Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
This study involves a two-part design. Part 1 is designed to evaluate the safety and tolerability of the 4 drug (HLX10+HLX04+carboplatin+pemetrexed). Part 2 is a randomized, open-label study, which will evaluate the safety and efficacy of HLX10 in combination with carboplatin+pemetrexed with or without HLX04(biosimilar of avastin) compared with treatment with carboplatin+pemetrexed in 1st line Stage IIIB/IIIC or IV non-squamous NSCLC. Participants will be randomized in a 1:1:1 ratio to Arm A (HLX10+HLX04+Carboplatin+Pemetrexed), Arm B (HLX10+HLX04 placebo+Carboplatin+Pemetrexed), or Arm C (HLX10 placebo + HLX04 placebo+Carboplatin+Pemetrexed).
Interventions
DRUGHLX10, an engineered anti-PD-1 antibody
HLX10 will be administered as IV infusion at a dose of 4.5mg/kg on Day 1 of each 21-day cycle until loss of clinical benefit or up to 2 year.
DRUGHLX04, a bevacizumab biosimilar
HLX04 will be administered as IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle until progressive disease, unacceptable toxicity, death or up to 2 year.
DRUGCarboplatin
Carboplatin will be administered at area under the concentration-time curve (AUC) 5 on Day 1 of each 21-day cycle for 4 cycles, or until loss of clinical benefit whichever occurs first.
DRUGPemetrexed
Pemetrexed will be administered as IV infusion at a dose of 500 milligrams per square meter (mg/m2) on Day 1 of each 21-day cycle until progressive disease, unacceptable toxicity, death or up to 2 year.
Sponsors
Shanghai Henlius Biotech
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed, Stage IIIB/IIIC or IV non-squamous NSCLC 2. Participants with no EGFR, ALK and ROS1 mutation. 3. Participants with no prior treatment for Stage IIIB/IIIC or IV non-squamous NSCLC 4. Measurable disease as defined by RECIST v1.1 5. Eastern Cooperative Oncology Group performance status 0 or 1 6. Adequate hematologic and end organ function
Exclusion criteria
1. Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome 2. Active central nervous system metastases 3. Prior treatment with cluster of differentiation immune checkpoint blockade therapies or Bevacizumab 4. Has received a surgical operation within 4 weeks from the initial drug administration 5. Active or suspected autoimmune diseases. Subjects in a stable state with no need for systemic immunosuppressant therapy are allowed to enroll. 6. Currently having or have had interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis and severe impaired pulmonary function that may interfere with the detection and management of suspected drug-related pulmonary toxicity 7. Any active infection requiring systemic anti-infective therapy within 14 days prior to study drug administration 8. Uncontrollable active infection(s) 9. History of immunodeficiency, including HIV antibody positive 10. active hepatitis B; or hepatitis C virus infections 11. Has bleeding tendency 12. History of severe cardiovascular diseases 13. Known gastrointestinal diseases as follows, Gastrointestinal perforation, abdominal fistula or abdominal abscess within 6 months before signing the informed consent; History of poorly controlled or recurrent inflammatory bowel disease; Active peptic ulcers, or \> moderate esophageal varices 14. Pregnant or breastfeeding female
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1 Safety and tolerability of study treatment | baseline to 21 days |
| Part 2-Progression Free Survival (PFS) as Determined by the IRRC using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | Baseline until disease progression or death, whichever occurs first (up to approximately 24months) |
Secondary
| Measure | Time frame |
|---|---|
| Part 1-Overall survival (OS) | Baseline up to approximately 36months |
| Part 1 and Part 2-PFS (assessed by the investigator according to RECIST v1.1) in Part 1 and 2; PFS (assessed by IRRC according to RECIST v1.1) in Part 1 | Baseline until disease progression or death, whichever occurs first (up to approximately 36months) |
| Part 1 and 2-Objective response rate (ORR, assessed by IRRC and investigator according to RECIST v1.1 criteria) | Baseline up to approximately 36 months |
| Part 1 and 2-Duration of response (DOR, assessed by IRRC and investigator according to RECIST v1.1 criteria) | Baseline up to approximately 36 months |
| Part 2-PFS2 (assessed by IRRC) | Baseline up to approximately 36months |
| Part 2-Overall survival (OS), as a major secondary endpoint | Baseline until death (up to approximately 36 months) |
| Part 1 and 2-Immunogenicity evaluation: positive anti-drug antibody (ADA) rate | Baseline up to approximately 36 months |
| Part 1 and 2-PD-L1 expression level | Baseline |
| Part 1 and 2-Microsatellite instability(MSI) | Baseline |
| Part 1 and 2-Tumor mutation burden(TMB) | Baseline |
| Part 1 and 2-Pharmacokinetics (PK): serum HLX10 concentration | Baseline up to approximately 36 months |
| Part 1 and 2-Incidence rates of AEs and SAEs | Baseline up to approximately 36months |
Countries
China
Outcome results
None listed