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)

• Sponsor: Shanghai Henlius Biotech
• Information provided by (Responsible Party): Shanghai Henlius Biotech

Study Description

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 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).

Condition or disease	Intervention/treatment	Phase
Carcinoma; Non-Small-Cell Lung	Drug: HLX10, an engineered anti-PD-1 antibody; Drug: HLX04, a bevacizumab biosimilar; Drug: Carboplatin; Drug: Pemetrexed	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 636 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
• Estimated Study Start Date: July 30, 2019
• Estimated Primary Completion Date: August 30, 2021
• Estimated Study Completion Date: March 2, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed); 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.	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.; Drug: 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.; Drug: 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.; Drug: 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.
Experimental: Part 2-Arm A (HLX10+HLX04+Carboplatin+Pemetrexed); 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.	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.; Drug: 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.; Drug: 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.; Drug: 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.
Experimental: Part 2-Arm B (HLX10+Carboplatin+Pemetrexed); 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.	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.; Drug: 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.; Drug: 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.
Active Comparator: Part 2-Arm C (Carboplatin+Pemetrexed); 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.	Drug: 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.; Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: baseline to 21 days ]
2. Part 2-Progression Free Survival (PFS) as Determined by the IRRC using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Baseline until disease progression or death, whichever occurs first (up to approximately 24months) ]

Secondary Outcome Measures :

1. Part 1 and 2-Incidence rates of AEs and SAEs [ Time Frame: Baseline up to approximately 27months ]
2. Part 1 and 2-Overall Survival (OS) [ Time Frame: Baseline until death (up to approximately 36 months) ]
3. 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) ]
4. 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 ]
5. 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 ]
6. Part 1 and 2-Pharmacokinetics (PK): serum HLX10 concentration [ Time Frame: Baseline up to approximately 25 months ]
7. Part 1 and 2-Immunogenicity evaluation: positive anti-drug antibody (ADA) rate [ Time Frame: Baseline up to approximately 25 months ]
8. Part 1 and 2-PD-L1 expression level [ Time Frame: Baseline ]
9. Part 1 and 2-Microsatellite instability(MSI) [ Time Frame: Baseline ]
10. Part 1 and 2-Tumor mutation burden(TMB) [ Time Frame: Baseline ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
2. Participants with no EGFR, ALK and ROS1 mutation.
3. Participants with no prior treatment for Stage 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

Contacts and Locations

Contacts

Contact: Jack Shan; +86 158 1071 2378; yong_shan@henlius.com

Contact: Peipei Zai; +86 155 2206 7076; peipei_zhai@henlius.com

Sponsors and Collaborators

Shanghai Henlius Biotech

Investigators

• Principal Investigator: Yankai Shi, professor; Cancer Hospital Chinese Academy of Medical Sciences (CAMS)

More Information

• Responsible Party: Shanghai Henlius Biotech
• ClinicalTrials.gov Identifier: NCT03952403 History of Changes
• Other Study ID Numbers: HLX10-002-NSCLC301
• First Posted: May 16, 2019
• Last Update Posted: May 20, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Bevacizumab; Carboplatin; Pemetrexed; Antibodies; Immunoglobulins; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Immunologic Factors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors