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

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 (NSCLC) With Negative Driver Genes and Failed Immunotherapy

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.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Cadonilimab (AK104)

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.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xinhua Xu, Master; Phone Number: +8613986747496; Email: 2732774352@qq.com
• Study Contact Backup: Name: Xinhua Xinhua, Master; Phone Number: +8613986747496; Email: 2732774352@qq.com

Study Locations

• China
  • Yichang, China, 443002
    • Recruiting
    • Department of Medical Oncology, Central Hospital of Yichang City, the First Clinical Medical College of Three Gorges University
    • Contact: Xinhua Xu, Master; Phone Number: +8613986747496; Email: 2732774352@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Bispecific antibody plus Chemotherapy

Drug: Cadonilimab (AK104); 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate（ORR）	The objective response rate (ORR) refers to the proportion of patients whose tumor shrinks by a certain percentage (generally 30%) and maintains this reduction for a certain period of time (generally 4 weeks).	approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	Disease Control Rate (DCR) is defined as the proportion of patients with a cancer or tumor who experience a reduction in the size of the disease, no progression of the disease, or stable disease conditions for a specified period of time after receiving a particular treatment. This typically includes patients who achieve complete response (CR), partial response (PR), or stable disease (SD).	approximately 24 months
Duration of Response (DoR)	Duration of Response (DoR), which stands for Duration of Response, refers to the length of time from the point when a subject achieves a confirmed complete response (CR) or partial response (PR) to the time when the first sign of disease progression or death due to any cause occurs.	approximately 24 months
Progression-free survival (PFS)	PFS was defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using response evaluation criteria In solid tumors (RECIST) v1.1.	approximately 24 months
Overall Survival (OS)	Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause.Data for participants who were not reported as dead at the time of analysis was censored at the date when they were last known to be alive.	approximately 24 months
Adverse event (AE)	Adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.	approximately 24 months

Collaborators and Investigators

• Sponsor: Xin-Hua Xu

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: June 16, 2024
• First Submitted That Met QC Criteria: June 16, 2024
• First Posted (Actual): June 21, 2024

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 16, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: CTGU010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No