Clinical trial NCT03952403: A Study of HLX10 in Combination With Carboplatin Plus (+) Pemetrexed With or Without HLX04 Compared With Carboplatin+Pemetrexed in 1L Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
Official title: A Three Arm, Randomized, Double-Blind, Multicenter, Phase 3 Study of HLX10(Anti-PD-1 Antibody) in Combination With Carboplatin Plus (+) Pemetrexed With or Without HLX04(Avastin Biosimilar) Compared With Carboplatin+Pemetrexed in 1L Stage IIIB/IIIC or IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Carcinoma
Non-Small-Cell Lung
Lead sponsor: Shanghai Henlius Biotech
Sponsor class: INDUSTRY
First posted: 2019-05-16
Enrollment: 643
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 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).


Eligibility criteria: 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

Primary outcomes:
measure: Part 1 Safety and tolerability of study treatment
timeFrame: baseline to 21 days
measure: Part 2-Progression Free Survival (PFS) as Determined by the IRRC using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Baseline until disease progression or death, whichever occurs first (up to approximately 24months)
Secondary outcomes:
measure: Part 2-Overall survival (OS), as a major secondary endpoint
timeFrame: Baseline until death (up to approximately 36 months)
measure: Part 1 and 2-Incidence rates of AEs and SAEs
timeFrame: Baseline up to approximately 36months
measure: Part 1-Overall survival (OS)
timeFrame: Baseline up to approximately 36months
measure: 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
timeFrame: Baseline until disease progression or death, whichever occurs first (up to approximately 36months)
measure: Part 1 and 2-Objective response rate (ORR, assessed by IRRC and investigator according to RECIST v1.1 criteria)
timeFrame: Baseline up to approximately 36 months
measure: Part 1 and 2-Duration of response (DOR, assessed by IRRC and investigator according to RECIST v1.1 criteria)
timeFrame: Baseline up to approximately 36 months
measure: Part 2-PFS2 (assessed by IRRC)
timeFrame: Baseline up to approximately 36months
measure: Part 1 and 2-Pharmacokinetics (PK): serum HLX10 concentration
timeFrame: Baseline up to approximately 36 months
measure: Part 1 and 2-Immunogenicity evaluation: positive anti-drug antibody (ADA) rate
timeFrame: Baseline up to approximately 36 months
measure: Part 1 and 2-PD-L1 expression level
timeFrame: Baseline
measure: Part 1 and 2-Microsatellite instability(MSI)
timeFrame: Baseline
measure: Part 1 and 2-Tumor mutation burden(TMB)
timeFrame: Baseline
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences (CAMS)
state: Beijing
Study officials:
affiliation: Cancer Hospital Chinese Academy of Medical Sciences (CAMS)
name: Yankai Shi, professor
role: PRINCIPAL_INVESTIGATOR
References: