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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

Primary Purpose

NSCLC Stage IV

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
HLX26
Serplulimab
Pemetrexed
Nab paclitaxel
Carboplatin
Sponsored by
Shanghai Henlius Biotech
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for NSCLC Stage IV

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The Affiliated Hospital of Xuzhou Medical UniversityRecruiting
  • Fudan University Shanghai Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

800mg dose level (Part 1)

1600mg dose level (Part 1)

800mg dose level (Part 2)

1600mg dose level (Part 2)

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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
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
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.

Secondary Outcome Measures

Disease Control Rate (DCR) per RECIST 1.1 as Assessed by Investigator
Progression Free Survival (PFS) per RECIST 1.1 assessed by Investigator
Duration of Response (DOR) per RECIST 1.1 assessed by Investigator
Overall Survival (OS)
Adverse events
The incidence of AE, SAE will be detected
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.
Immunogenicity of HLX26
The incidence of Anti-HLX26 antibody and the incidence of neutralizing antibody will be detected

Full Information

First Posted
March 3, 2023
Last Updated
August 16, 2023
Sponsor
Shanghai Henlius Biotech
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1. Study Identification

Unique Protocol Identification Number
NCT05787613
Brief Title
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
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 10, 2023 (Actual)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
July 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Henlius Biotech

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NSCLC Stage IV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
800mg dose level (Part 1)
Arm Type
Experimental
Arm Description
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.
Arm Title
1600mg dose level (Part 1)
Arm Type
Experimental
Arm Description
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.
Arm Title
800mg dose level (Part 2)
Arm Type
Experimental
Arm Description
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.
Arm Title
1600mg dose level (Part 2)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
HLX26
Other Intervention Name(s)
Anti-LAG-3 monoclonal Antibody Injection
Intervention Description
Anti-LAG-3 monoclonal Antibody Injection
Intervention Type
Drug
Intervention Name(s)
Serplulimab
Other Intervention Name(s)
HLX10
Intervention Description
anti-PD-1 humanized monoclonal antibody injection
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Description
non-squamous NSCLC patients will receive Pemetrexed treatment
Intervention Type
Drug
Intervention Name(s)
Nab paclitaxel
Intervention Description
squamous NSCLC patients will receive nab-Paclitaxel treatment
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
non-squamous and squamous NSCLC patients will receive Carboplatin treatment
Primary Outcome Measure Information:
Title
Dose-limiting toxicity (DLT) (Part 1)
Description
The DLT of HLX26 in combination with Serplulimab and Chemotherapy within 3 weeks after the first administration in previously untreated NSCLC patients
Time Frame
from day1 to day 21
Title
Maximum Tolerated Dose (MTD) (Part 1)
Description
The MTD of HLX26 in combination with Serplulimab and Chemotherapy within 3 weeks after the first administration in previously untreated NSCLC patients
Time Frame
from day1 to day 21
Title
Objective Response Rate (ORR) per RECIST 1.1 as Assessed by Investigator ( Part 2)
Description
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.
Time Frame
approximately up to 12 months
Secondary Outcome Measure Information:
Title
Disease Control Rate (DCR) per RECIST 1.1 as Assessed by Investigator
Time Frame
approximately up to 12 months
Title
Progression Free Survival (PFS) per RECIST 1.1 assessed by Investigator
Time Frame
approximately up to 12 months
Title
Duration of Response (DOR) per RECIST 1.1 assessed by Investigator
Time Frame
approximately up to 12 months
Title
Overall Survival (OS)
Time Frame
approximately up to 36 months
Title
Adverse events
Description
The incidence of AE, SAE will be detected
Time Frame
approximately up to 12 months
Title
Serum concentration of HLX26 and Serplulimab
Description
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.
Time Frame
approximately up to 12 months
Title
Immunogenicity of HLX26
Description
The incidence of Anti-HLX26 antibody and the incidence of neutralizing antibody will be detected
Time Frame
approximately up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yongqing LIN
Phone
021-33395800
First Name & Middle Initial & Last Name or Official Title & Degree
Dongqing LIU
Phone
021-33395800
Facility Information:
Facility Name
The Affiliated Hospital of Xuzhou Medical University
City
Xuzhou
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bi CHEN
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jialei WANG
First Name & Middle Initial & Last Name & Degree
Jialei WANG

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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