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)

Carcinoma Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03952403
• Other study ID #: HLX10-002-NSCLC301
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 2, 2019
• Est. completion date: March 15, 2024

Study information

• Verified date: August 2023
• Source: Shanghai Henlius Biotech
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 643
• Est. completion date: March 15, 2024
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Non-Small-Cell Lung

Intervention

Drug:
• HLX10, 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.
• HLX04, 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.
• Carboplatin
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.
• Pemetrexed
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.

Locations

Country	Name	City	State
China	Cancer Hospital Chinese Academy of Medical Sciences (CAMS)	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Henlius Biotech

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 Safety and tolerability of study treatment		baseline to 21 days
Primary	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	Part 2-Overall survival (OS), as a major secondary endpoint		Baseline until death (up to approximately 36 months)
Secondary	Part 1 and 2-Incidence rates of AEs and SAEs		Baseline up to approximately 36months
Secondary	Part 1-Overall survival (OS)		Baseline up to approximately 36months
Secondary	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)
Secondary	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
Secondary	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
Secondary	Part 2-PFS2 (assessed by IRRC)		Baseline up to approximately 36months
Secondary	Part 1 and 2-Pharmacokinetics (PK): serum HLX10 concentration		Baseline up to approximately 36 months
Secondary	Part 1 and 2-Immunogenicity evaluation: positive anti-drug antibody (ADA) rate		Baseline up to approximately 36 months
Secondary	Part 1 and 2-PD-L1 expression level		Baseline
Secondary	Part 1 and 2-Microsatellite instability(MSI)		Baseline
Secondary	Part 1 and 2-Tumor mutation burden(TMB)		Baseline