A Prospective, Open-label, Single-center, Single-arm Phase II Clinical Study of Cadonilimab (AK104) Combined With Monotherapy Chemotherapy in Patients With Advanced Non-small Cell Lung Cancer With Negative Driver Genes and Failed Immunotherapy

Trial Title: A Prospective, Open-label, Single-center, Single-arm Phase II Clinical Study of Cadonilimab (AK104) Combined With Monotherapy Chemotherapy in Patients With Advanced Non-small Cell Lung Cancer With Negative Driver Genes and Failed Immunotherapy

NCT ID: NCT06467500

Condition: Non-small Cell Lung Cancer

Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Cadonilimab (AK104)
Description: Subjects participated in a study where they received cadonilimab intravenously at 6mg/kg every two weeks, prepared in 100mL of normal saline (0.9% NaCl), with a final concentration range of 0.2-5.0mg/mL. The infusion solution must be used within 4 hours of preparation. Treatment continued until disease progression (PD), unacceptable toxicity, or 24 months, whichever came first. Patients who investigators deemed could still benefit from cadonilimab post-PD were allowed continued treatment. Chemotherapy regimens were selected by investigators based on prior medication use, including gemcitabine, pemetrexed, docetaxel, albumin-bound paclitaxel, or vinorelbine as second- or third-line therapy
Arm group label: Bispecific antibody plus Chemotherapy

Summary: The aim of evaluating the efficacy and safety of cadonilimab combined with monotherapy chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with negative driver genes who have failed previous immunotherapy is to provide a more effective and safe treatment option for these patients.

Detailed description: Cadonilimab (AK104), China's first globally developed bispecific antibody targeting both PD-1 and CTLA-4, has demonstrated manageable safety and promising anti-tumor activity in female cervical cancer, esophageal squamous cell carcinoma, and hepatocellular carcinoma. However, there is currently no available data on the efficacy and safety of cadonilimab combined with monotherapy chemotherapy for treating advanced non-small cell lung cancer (NSCLC) with negative driver genes and previous immunotherapy failure. Therefore, this study aims to prospectively and openly evaluate the efficacy and safety of cadonilimab combined with monotherapy chemotherapy in treating patients with advanced NSCLC with negative driver genes and previous immunotherapy failure using a single-arm trial design. The goal is to provide a more effective and safe treatment option for these patients.

Criteria for eligibility:
Criteria:
Inclusion Criteria: Voluntarily participate in clinical research; Fully understand and be informed of this study and sign the informed consent form; 1. Age ≥ 18 and ≤ 75, male or female; 2. ECOG physical performance score of 0-2; 3. Patients with histologically confirmed squamous or non-squamous advanced non- small cell lung cancer (according to AJCC, 8th edition); 4. Patients who tested negative for driver genes after genetic testing; 5. Patients who have undergone previous systemic therapy and failed anti-PD-1/PD- L1 immunotherapy; 6. Presence of at least one measurable lesion as defined by Recist criteria 1.1; 7. Liver function: Total serum bilirubin ≤ 1.5 × ULN; For subjects without liver metastasis, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, and for those with liver metastasis, ALT and AST ≤ 5 × ULN; 8. Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 45 mL/min (using the Cockcroft/Gault formula); Blood routine: Absolute neutrophil count ≥ 1.5 × 109/L, platelet count ≥ 70 × 109/L; Hemoglobin ≥ 80g/L (no blood transfusion or use of hematopoietic stimulating drugs for correction within 7 days before screening) with an expected lifespan of more than 3 months. Exclusion Criteria: 1. ECOG physical performance score > 2; 2. Previous treatment with bispecific antibodies; 3. Participation in other clinical trials within 30 days prior to screening; 4. Tumor metastasis to the brain and/or leptomeninges; 5. History of other malignancies (excluding cervical carcinoma in situ or skin basal cell carcinoma that has been cured, and other malignancies that have been cured for more than 5 years); 6. Accompanied by other serious diseases, including but not limited to: 1. Difficult-to-control congestive heart failure (NYHA class III or IV), unstable angina, poorly controlled arrhythmia, uncontrolled moderate to severe hypertension (SBP > 160mmHg or DBP > 100mmHg); 2. Severe active infection; 3. Difficult-to-control diabetes (referring to large fluctuations in blood sugar despite standard insulin therapy and frequent blood glucose monitoring, affecting the patient's life and frequently causing hypotension); 4. Mental illness affecting informed consent and/or protocol compliance. 7. Allergy to the drugs used in this protocol or their ingredients; 8. Pregnant (confirmed by blood or urine HCG testing) or breastfeeding women, or subjects of reproductive age who are unwilling or unable to take effective contraceptive measures (applicable to both male and female subjects) until at least 6 months after the last experimental treatment; 9. Investigators consider it inappropriate to participate in this study; 10. Unwilling to participate in this study or unable to sign the informed consent form.

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: Department of Medical Oncology, Central Hospital of Yichang City, the First Clinical Medical College of Three Gorges University

Address:
City: Yichang
Zip: 443002
Country: China

Status: Recruiting

Contact:
Last name: Xinhua Xu, Master

Phone: +8613986747496
Email: 2732774352@qq.com

Start date: March 1, 2024

Completion date: December 30, 2026

Lead sponsor:
Agency: Xin-Hua Xu
Agency class: Other

Source: China Three Gorges University, Yichang, China

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06467500