Cadonilimab (AK104) Plus Chemotherapy as First-line Treatment in Non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients With Programmed Cell Death Ligand 1 (PD-L1) Negative

Study Overview
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Brief Summary
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This is a single arm, multi-center clinical trial. Target population is advanced or metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients with Programmed Cell Death Ligand 1 (PD-L1) negative, aiming to evaluate the efficacy and safety of the combination therapy of Cadonilimab and chemotherapy. Cadonilimab is a PD-1/CTLA-4 bi-specific antibody.

Detailed Description
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This trial enrolled advanced or metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients with Programmed Cell Death Ligand 1 (PD-L1) negative. Patients will receive cadonilimab (10mg/kg) plus pemetrexed(500mg/m2) and carboplatin (AUC=5) every 3 weeks for 4 cycles, follwed with cadonilimab (10mg/kg) plus pemetrexed (500mg/m2) every 3 weeks as maintenance therapy. The primary endpoint is 12-month progression-free-survival (PFS) rate assessed by investigators. Key secondary endpoints include objective response rate (ORR), duration of response (DOR), disease control rate (DCR), time to response (TTR), progression free survival (PFS), overall survival (OS), and safety.

Official Title
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Cadonilimab (AK104) Plus Chemotherapy as First-line Treatment in Non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients With Programmed Cell Death Ligand 1 (PD-L1) Negative：A Multi-center, Single-arm, Phase II Study

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Cadonilimab
* Drug: Pemetrexed
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically/cytologically stage IIIB, IIIC, IV non-squamous Non-Small Cell Lung Cancer (NSCLC) PD-L1 TPS<1% Life expectancy more than 3 months Without EGFR-sensitive mutation (19Exon del/21Exon L858R), ALK, ROS1 gene rearrangement or fusion Has no prior systemic therapy; (chemotherapy and/or radiotherapy is allowed as part of neoadjuvant/adjuvant therapy. Patients who have had recurrence or metastasis for more than 6 months from the end of neoadjuvant/adjuvant treatment would be enrolled) ECOG score 0-1 Patients must have at least one measurable lesion according to RECIST 1.1 Has adequate organ function Agree to provide tumour tissue samples for biomarker exploration (including but not limited to PD-L1 IHC or NGS testing) Voluntarily sign a written informed consent form Exclusion Criteria: Histological examination with Small Cell Lung Cancer or squamous Non-Small Cell Lung Cancer With active central nervous system (CNS) metastases confirmed by CT or MRI With other malignancy within 3 years before enrollment With severe infections within 4 weeks of the first dose of study treatment Women who are pregnant or lactating History of interstitial lung disease, drug-induced interstitial lung disease, or radiation pneumonia requiring hormone therapy History of myocarditis, cardiomyopathy, and malignant arrhythmia Tumor compresses important surrounding organs (such as the esophagus) with accompanying symptoms, compressing the superior vena cava or invading the mediastinal vessels, heart, etc. Risk of bleeding, major hemoptysis, or with history of coagulation dysfunction Active autoimmune diseases that require systematic treatment within 2 years before enrollment History of Human Immunodeficiency Virus (HIV) With active hepatitis B infection With uncontrollable pleural effusion, pericardial effusion, or ascites that require repeated drainage

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>Patients will receive cadonilimab (10mg/kg) plus pemetrexed(500mg/m2) and carboplatin (AUC=5) every 3 weeks for 4 cycles, follwed with cadonilimab (10mg/kg) plus pemetrexed (500mg/m2) every 3 weeks as maintenance therapy. | Drug: Cadonilimab<br>* Patients receive cadonilimab (10mg/kg) every 3 weeks.<br>* Other names: AK104;Drug: Pemetrexed<br>* Patients receive pemetrexed (500mg/m2) every 3 weeks.<br>Drug: Carboplatin<br>* Patients receive carboplatin (AUC=5) every 3 weeks for 4 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-month progression-free-survival (PFS) rate | Rate of patients with complete/partial response at 12-month from enrollment | At 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate (ORR) | objective response rate using RECIST 1.1 criteria | about 24 months | 
| duration of response (DOR) | Time from the date of the first documented response (CR or PR) to the earliest date of disease progression (RECIST 1.1), or death due to any cause | about 24 months | 
| disease control rate (DCR) | disease control rate using RECIST 1.1 criteria | about 24 months | 
| time to response (TTR) | Time from the date of enrollment to the first documented response (CR or PR) (RECIST 1.1) | about 24 months | 
| progression free survival (PFS) | Time from enrollment to first observation of progression (RECIST1.1) or date of death (from any cause) | about 24 months | 
| overall survival (OS) | Time from enrollment until death due to any cause | about 24 months | 
| incidence, type and severity of adverse events | Descriptive statistics of safety will be presented using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 | From time of informed consent through treatment period and up to 30 days post last dose of study treatment (about 24 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-squamous Non-Small Cell Lung Cancer, Programmed Cell Death Ligand 1, cadonilimab