Clinical trial NCT06001151: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: non-squamous Non-Small Cell Lung Cancer
Programmed Cell Death Ligand 1
cadonilimab
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: Akeso Pharmaceuticals, Inc.
First posted: 2023-08-21
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 12-month progression-free-survival (PFS) rate
timeFrame: At 12 months
Secondary outcomes:
measure: objective response rate (ORR)
timeFrame: about 24 months
measure: duration of response (DOR)
timeFrame: about 24 months
measure: disease control rate (DCR)
timeFrame: about 24 months
measure: time to response (TTR)
timeFrame: about 24 months
measure: progression free survival (PFS)
timeFrame: about 24 months
measure: overall survival (OS)
timeFrame: about 24 months
measure: incidence, type and severity of adverse events
timeFrame: From time of informed consent through treatment period and up to 30 days post last dose of study treatment (about 24 months)
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Qian Chu
state: Hubei
Study officials:
affiliation: Tongji Hospital
name: Qian Chu
role: PRINCIPAL_INVESTIGATOR
References: