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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: NSCLC Stage IV
• Intervention / Treatment: Drug: Placebo; Drug: HLX26; Drug: Serplulimab; Drug: Chemotherapy drug

Detailed Description

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 trial was divided into period 1 (safety run-in phase) and period 2 (dose expansion phase).

The first phase is an open-label study, patients will receive varying doses (800 mg, 600 mg or lower) of HLX26 combined with a fixed dose (300 mg) of serplulimab and chemotherapy, administered by intravenous infusion 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 combined with Serplulimab and chemotherapy will be evaluated in period 2.

The second phase (dose expansion phase) is a randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of 2 dose levels of HLX26 combined with fixed-dose (300 mg) of serplulimab and chemotherapy in patients with NSCLC. If the tolerability observation of the 600mg dose group is completed in the first phase, the SRC will review the safety data obtained from the study and decide whether to enter into the second phase; if 2 of the 6 subjects in the 600mg dose group in the first phase occur DLT event, we will continue to explore the safe dose of HLX26 and enroll another 3-6 subjects. Once the maximum tolerated dose (MTD) is found, two doses, MTD and MTD-1, will be selected to enter the dose expansion phase. (The SRC will review the safety and tolerability results obtained in the study to determine the MTD, and will select the dose of MTD-1 below the MTD and within the effective dose range). In the second stage, there are 3 groups and 40 people in each group. The interactive network/voice response system (IWRS) is used to randomly assign qualified subjects to the following three groups in a 1:1:1 allocation ratio:

> Group A: HLX26 MTD intravenous infusion + serplulimab 300 mg intravenous infusion, Q3W; chemotherapy

> Group B: HLX26 MTD-1 intravenous infusion + serplulimab 300 mg intravenous infusion, Q3W; chemotherapy

> Group C: placebo + serplulimab 300 mg intravenous infusion, Q3W; chemotherapy

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 or paclitaxel and carboplatin.

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China
      • The Affiliated Hospital of Xuzhou Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China
      • Shanghai Chest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Stage IV (AJCC 8th Edition) non-small cell lung cancer confirmed by histology or cytology.
2. No EGFR sensitive mutation or ALK, ROS1 rearrangement.
3. 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.
4. At least one measurable lesion evaluated by the investigator per RECIST v1.1.
5. Subjects must provide qualified tumor tissue samples for the detection of PD-L1 and LAG-3 expression level.
6. Have adequate organ function with expected survival period ≥ 12 weeks and ECOG score of 0 or 1.

Key Exclusion Criteria:

1. Subjects with other histopathological types including small cell lung cancer, neuroendocrine cancer or sarcoma.
2. Have other malignant tumors within 3 years.
3. Pleural effusion, pericardial effusion or ascites that require clinical intervention.
4. Myocardial infarction and poorly controlled arrhythmia occurred within six months before the first administration of the study drug.
5. III - IV cardiac insufficiency per NYHA standard or left ventricular ejection fraction<50%.
6. Patients with active pulmonary tuberculosis.
7. 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.
8. 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.
9. 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.
10. 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.
11. Patients with a history of severe allergy to any monoclonal antibody products.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLX26 MTD + serplulimab 300 mg + chemotherapy intravenous infusion Q3W; In this group, HLX26 (MTD) in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 40 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 (MTD) in combination with Serplulimab and chemotherapy will be evaluated in this group.	Drug: HLX26; Anti-LAG-3 monoclonal Antibody Injection; Other Names: Anti-LAG-3 monoclonal Antibody Injection; Drug: Serplulimab; anti-PD-1 humanized monoclonal antibody injection; Other Names: HLX10; Drug: Chemotherapy drug; non-squamous NSCLC patients will receive Pemetrexed 500mg/m2, IV, Q3W. Carboplatin AUC 5mg/mL/min, IV, Q3W, up to 4 cycles.squamous NSCLC patients will receive Albumin-paclitaxel 100mg/m2, IV, Q1W or paclitaxel 175mg/m2, IV, Q3W and carboplatin AUC 5 mg/mL/min, IV, Q3W, up to 4 cycles.
Experimental: HLX26 MTD-1 + serplulimab 300 mg + chemotherapy intravenous infusion Q3W; In this group, HLX26 (MTD-1) in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 40 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 (MTD-1) in combination with Serplulimab and chemotherapy will be evaluated in this group.	Drug: HLX26; Anti-LAG-3 monoclonal Antibody Injection; Other Names: Anti-LAG-3 monoclonal Antibody Injection; Drug: Serplulimab; anti-PD-1 humanized monoclonal antibody injection; Other Names: HLX10; Drug: Chemotherapy drug; non-squamous NSCLC patients will receive Pemetrexed 500mg/m2, IV, Q3W. Carboplatin AUC 5mg/mL/min, IV, Q3W, up to 4 cycles.squamous NSCLC patients will receive Albumin-paclitaxel 100mg/m2, IV, Q1W or paclitaxel 175mg/m2, IV, Q3W and carboplatin AUC 5 mg/mL/min, IV, Q3W, up to 4 cycles.
Placebo Comparator: placebo + serplulimab 300 mg + chemotherapy intravenous infusion Q3W; In this group, placebo in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 40 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 Serplulimab and chemotherapy will be evaluated in this group.	Drug: Placebo; placebo; Drug: Serplulimab; anti-PD-1 humanized monoclonal antibody injection; Other Names: HLX10; Drug: Chemotherapy drug; non-squamous NSCLC patients will receive Pemetrexed 500mg/m2, IV, Q3W. Carboplatin AUC 5mg/mL/min, IV, Q3W, up to 4 cycles.squamous NSCLC patients will receive Albumin-paclitaxel 100mg/m2, IV, Q1W or paclitaxel 175mg/m2, IV, Q3W and carboplatin AUC 5 mg/mL/min, IV, Q3W, up to 4 cycles.

What is the study measuring?

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 IRRC ( 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 IRRC.	approximately up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Progression Free Survival (PFS) per RECIST 1.1 assessed by IRRC and Investigator		approximately up to 12 months
Disease Control Rate (DCR) per RECIST 1.1 as Assessed by IRRC and Investigator		approximately up to 12 months
Duration of Response (DOR) per RECIST 1.1 assessed by IRRC and Investigator		approximately up to 12 months
Objective Response Rate (ORR) per RECIST 1.1 assessed by Investigator	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

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2023
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: March 3, 2023
• First Submitted That Met QC Criteria: March 15, 2023
• First Posted (Actual): March 28, 2023

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Immunologic Factors; Physiological Effects of Drugs; Antibodies, Monoclonal
• Other Study ID Numbers: HLX26HLX10-NSCLC201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No