A Clinical Study to Evaluate the Efficacy and Safety of HLX26 (Anti-LAG-3 Monoclonal Antibody Injection) Combined With Serplulimab and Chemotherapy in Previously Untreated Advanced NSCLC Patients

Study Overview
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Brief Summary
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A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of HLX26 (Anti-LAG-3 Monoclonal Antibody Injection) Combined With Serplulimab (Anti-PD-1 Humanized Monoclonal Antibody Injection) and Chemotherapy in Previously Untreated Advanced Non-small Cell Lung Cancer (NSCLC) Patients

Detailed Description
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This study is a phase II study to evaluate the efficacy, safety and tolerability of HLX26 in combination with Serplulimab and chemotherapy in the treatment of patients with Non-small cell lung cancer. The study is composed of the Part 1 (dose escalation) and Part 2 (dose expansion). In Part 1, a 3 + 3 dose escalation design will be used. Patients will receive HLX26 (800mg or 1600mg) combined with fixed dose (300mg) Serplulimab and chemotherapy intravenously every 3 weeks. Observation period of DLT lasts for 3 weeks after the first administration of HLX26. Safety review committee (SRC) will responsible for the safety of combination treatment. After confirmation of the safety, the efficacy of HLX26 (800mg or 1600mg) combined with Serplulimab and chemotherapy will be evaluated in Part 2. Eligible subjects will be enrolled in the HLX26 800mg group and HLX26 1600mg group in sequence. The chemotherapy will be decided by investigator per patients' pathological type. nsqNSCLC patients will receive pemetrexed and carboplatin as chemotherapy and sqNSCLC patients will receive nab-paclitaxel and carboplatin. About 60 patients will be enrolled in total.

Official Title
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A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of HLX26 (Anti-LAG-3 Monoclonal Antibody Injection) Combined With Serplulimab (Anti-PD-1 Humanized Monoclonal Antibody Injection) and Chemotherapy in Previously Untreated Advanced Non-small Cell Lung Cancer (NSCLC) Patients

Conditions
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NSCLC Stage IV

Intervention / Treatment
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* Drug: HLX26
* Drug: Serplulimab
* Drug: Pemetrexed
* Drug: Nab paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Stage IV (AJCC 8th Edition) non-small cell lung cancer confirmed by histology or cytology. No EGFR sensitive mutation or ALK, ROS1 rearrangement. Have not received systemic treatment for stage IV disease. For patients who have received adjuvant or neoadjuvant treatment, if the adjuvant/neoadjuvant treatment has been completed for at least 6 months, they are allowed to be enrolled. At least one measurable lesion evaluated by the investigator per RECIST v1.1. Subjects must provide qualified tumor tissue samples for the detection of PD-L1 and LAG-3 expression level. Have adequate organ function with expected survival period ≥ 12 weeks and ECOG score of 0 or 1. Key Exclusion Criteria: Subjects with other histopathological types including small cell lung cancer, neuroendocrine cancer or sarcoma. Have other malignant tumors within 3 years. Pleural effusion, pericardial effusion or ascites that require clinical intervention. Myocardial infarction and poorly controlled arrhythmia occurred within six months before the first administration of the study drug. III - IV cardiac insufficiency per NYHA standard or left ventricular ejection fraction<50%. Patients with active pulmonary tuberculosis. Patients with previous or current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severe pulmonary function impairment that may interfere with the detection and management of suspected drug-related pulmonary toxicity. Patients who have known active autoimmune diseases or suspected auto-immue disease. Patients in stable condition and do not require systemic immunosuppressant therapy are allowed to be enrolled. Require systemic treatment with corticosteroids (> 10 mg/day prednisone or equivalent) or other immunosuppressive agents within 14 days prior to the first dose of the study products or during the study. Patients who have received any T-cell costimulatory agents or immune checkpoint blockade therapy, including but not limited to cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors, PD-1 inhibitors, PD-L1 inhibitors. Patients with a history of severe allergy to any monoclonal antibody products.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 800mg dose level (Part 1)<br>In this group, HLX26 (800 mg) in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. The observation period of DLT events is within 3 weeks after the first administration of HLX26. 3 to 6 subjects will be enrolled in this cohort (per DLT occurrence). Patients will be treated with until disease progression, death, receiving new antitumor treatment, intolerable toxicity or withdrawal of informed consent (whichever occurs first). The safety of HLX26 (800 mg) in combination with Serplulimab and chemotherapy will be evaluated in this group. | Drug: HLX26<br>* Anti-LAG-3 monoclonal Antibody Injection<br>* Other names: Anti-LAG-3 monoclonal Antibody Injection;Drug: Serplulimab<br>* anti-PD-1 humanized monoclonal antibody injection<br>* Other names: HLX10;Drug: Pemetrexed<br>* non-squamous NSCLC patients will receive Pemetrexed treatment<br>Drug: Nab paclitaxel<br>* squamous NSCLC patients will receive nab-Paclitaxel treatment<br>Drug: Carboplatin<br>* non-squamous and squamous NSCLC patients will receive Carboplatin treatment<br>|
| Experimental: 1600mg dose level (Part 1)<br>In this group, HLX26 (1600 mg) in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. The observation period of DLT events is within 3 weeks after the first administration of HLX26. 3 to 6 subjects will be enrolled in this cohort (per DLT occurrence). Patients will be treated with until disease progression, death, receiving new antitumor treatment, intolerable toxicity or withdrawal of informed consent (whichever occurs first). The safety of HLX26 (1600 mg) in combination with Serplulimab and chemotherapy will be evaluated in this group. | Drug: HLX26<br>* Anti-LAG-3 monoclonal Antibody Injection<br>* Other names: Anti-LAG-3 monoclonal Antibody Injection;Drug: Serplulimab<br>* anti-PD-1 humanized monoclonal antibody injection<br>* Other names: HLX10;Drug: Pemetrexed<br>* non-squamous NSCLC patients will receive Pemetrexed treatment<br>Drug: Nab paclitaxel<br>* squamous NSCLC patients will receive nab-Paclitaxel treatment<br>Drug: Carboplatin<br>* non-squamous and squamous NSCLC patients will receive Carboplatin treatment<br>|
| Experimental: 800mg dose level (Part 2)<br>In this group, HLX26 (800 mg) in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 27 subjects will be enrolled in this cohort. Patients will be treated with until disease progression, death, receiving new antitumor treatment, intolerable toxicity or withdrawal of informed consent (whichever occurs first). The efficacy of HLX26 (800 mg) in combination with Serplulimab and chemotherapy will be evaluated in this group. | Drug: HLX26<br>* Anti-LAG-3 monoclonal Antibody Injection<br>* Other names: Anti-LAG-3 monoclonal Antibody Injection;Drug: Serplulimab<br>* anti-PD-1 humanized monoclonal antibody injection<br>* Other names: HLX10;Drug: Pemetrexed<br>* non-squamous NSCLC patients will receive Pemetrexed treatment<br>Drug: Nab paclitaxel<br>* squamous NSCLC patients will receive nab-Paclitaxel treatment<br>Drug: Carboplatin<br>* non-squamous and squamous NSCLC patients will receive Carboplatin treatment<br>|
| Experimental: 1600mg dose level (Part 2)<br>In this group, HLX26 (1600 mg) in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 27 subjects will be enrolled in this cohort. Patients will be treated with until disease progression, death, receiving new antitumor treatment, intolerable toxicity or withdrawal of informed consent (whichever occurs first). The efficacy of HLX26 (1600 mg) in combination with Serplulimab and chemotherapy will be evaluated in this group. | Drug: HLX26<br>* Anti-LAG-3 monoclonal Antibody Injection<br>* Other names: Anti-LAG-3 monoclonal Antibody Injection;Drug: Serplulimab<br>* anti-PD-1 humanized monoclonal antibody injection<br>* Other names: HLX10;Drug: Pemetrexed<br>* non-squamous NSCLC patients will receive Pemetrexed treatment<br>Drug: Nab paclitaxel<br>* squamous NSCLC patients will receive nab-Paclitaxel treatment<br>Drug: Carboplatin<br>* non-squamous and squamous NSCLC patients will receive Carboplatin treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) (Part 1) | The DLT of HLX26 in combination with Serplulimab and Chemotherapy within 3 weeks after the first administration in previously untreated NSCLC patients | from day1 to day 21 | 
| Maximum Tolerated Dose (MTD) (Part 1) | The MTD of HLX26 in combination with Serplulimab and Chemotherapy within 3 weeks after the first administration in previously untreated NSCLC patients | from day1 to day 21 | 
| Objective Response Rate (ORR) per RECIST 1.1 as Assessed by Investigator ( Part 2) | The ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by investigator. | approximately up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) per RECIST 1.1 as Assessed by Investigator |  | approximately up to 12 months | 
| Progression Free Survival (PFS) per RECIST 1.1 assessed by Investigator |  | approximately up to 12 months | 
| Duration of Response (DOR) per RECIST 1.1 assessed by Investigator |  | approximately up to 12 months | 
| Overall Survival (OS) |  | approximately up to 36 months | 
| Adverse events | The incidence of AE, SAE will be detected | approximately up to 12 months | 
| Serum concentration of HLX26 and Serplulimab | The serum concentration of HLX26 (at Cycle 1,2,4 and every 4 cycles from Cycle 8 and thereafter) and Serplulimab (at Cycle 4) will be detected. | approximately up to 12 months | 
| Immunogenicity of HLX26 | The incidence of Anti-HLX26 antibody and the incidence of neutralizing antibody will be detected | approximately up to 12 months |