Description:
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+Carboplatin+Pemetrexed), or Arm C
(Carboplatin+Pemetrexed).
Title
- Brief Title: A Study of HLX10 in Combination With Carboplatin Plus (+) Pemetrexed With or Without HLX04 Compared With Carboplatin+Pemetrexed in 1L Metastatic 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)
Clinical Trial IDs
- ORG STUDY ID:
HLX10-002-NSCLC301
- NCT ID:
NCT03952403
Conditions
- Carcinoma
- Non-Small-Cell Lung
Interventions
Drug | Synonyms | Arms |
---|
HLX10, an engineered anti-PD-1 antibody | | Part 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed) |
HLX04, a bevacizumab biosimilar | | Part 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed) |
Carboplatin | | Part 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed) |
Pemetrexed | | Part 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed) |
Purpose
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+Carboplatin+Pemetrexed), or Arm C
(Carboplatin+Pemetrexed).
Trial Arms
Name | Type | Description | Interventions |
---|
Part 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed) | Experimental | Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase. | - HLX10, an engineered anti-PD-1 antibody
- HLX04, a bevacizumab biosimilar
- Carboplatin
- Pemetrexed
|
Part 2-Arm A (HLX10+HLX04+Carboplatin+Pemetrexed) | Experimental | Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase. | - HLX10, an engineered anti-PD-1 antibody
- HLX04, a bevacizumab biosimilar
- Carboplatin
- Pemetrexed
|
Part 2-Arm B (HLX10+Carboplatin+Pemetrexed) | Experimental | Participants will receive IV infusion of HLX10 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase. | - HLX10, an engineered anti-PD-1 antibody
- Carboplatin
- Pemetrexed
|
Part 2-Arm C (Carboplatin+Pemetrexed) | Active Comparator | Participants will receive IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase. | |
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
Maximum Eligible Age: | 75 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |
Time Frame: | baseline to 21 days |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Part 1 and 2-Incidence rates of AEs and SAEs |
Time Frame: | Baseline up to approximately 27months |
Safety Issue: | |
Description: | |
Measure: | Part 1 and 2-Overall Survival (OS) |
Time Frame: | Baseline until death (up to approximately 36 months) |
Safety Issue: | |
Description: | |
Measure: | Part 1-PFS (assessed by the investigator according to RECIST v1.1) |
Time Frame: | Baseline until disease progression or death, whichever occurs first (up to approximately 36months) |
Safety Issue: | |
Description: | |
Measure: | Part 1 and 2-Objective response rate (ORR, assessed by IRRC and investigator according to RECIST v1.1 criteria) |
Time Frame: | Baseline up to approximately 24 months |
Safety Issue: | |
Description: | |
Measure: | Part 1 and 2-Duration of response (DOR, assessed by IRRC and investigator according to RECIST v1.1 criteria) |
Time Frame: | Baseline up to approximately 36 months |
Safety Issue: | |
Description: | |
Measure: | Part 1 and 2-Pharmacokinetics (PK): serum HLX10 concentration |
Time Frame: | Baseline up to approximately 25 months |
Safety Issue: | |
Description: | |
Measure: | Part 1 and 2-Immunogenicity evaluation: positive anti-drug antibody (ADA) rate |
Time Frame: | Baseline up to approximately 25 months |
Safety Issue: | |
Description: | |
Measure: | Part 1 and 2-PD-L1 expression level |
Time Frame: | Baseline |
Safety Issue: | |
Description: | |
Measure: | Part 1 and 2-Microsatellite instability(MSI) |
Time Frame: | Baseline |
Safety Issue: | |
Description: | |
Measure: | Part 1 and 2-Tumor mutation burden(TMB) |
Time Frame: | Baseline |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Shanghai Henlius Biotech |
Last Updated
May 12, 2020