Combining Cadonilimab with Chemotherapy for PD-L1 Negative Lung Cancer

A Phase II Clinical Study of Cadonilimab in Combination With Chemotherapy as First-Line Treatment for PD-L1 Negative Advanced Non-Small Cell Lung Cancer

This study is testing if combining a new drug called Cadonilimab with chemotherapy can help people with advanced lung cancer that has a specific negative marker feel better and live longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Shanghai Pulmonary Hospital, Shanghai, China (other)
• Drugs / interventions: Cadonilimab, chemotherapy, methotrexate, cyclophosphamide, prednisone
• Locations: 2 sites (Shanghai, Shanghai Municipality and 1 other locations)
• Trial ID: NCT06424821 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness and safety of a combination treatment using Cadonilimab, a PD-1/CTLA-4 inhibitor, alongside chemotherapy as a first-line therapy for patients with PD-L1 negative advanced non-small cell lung cancer (NSCLC). The study is a multi-center, open-label, single-arm phase II trial where participants will receive Cadonilimab and platinum-based chemotherapy for up to four cycles, followed by maintenance therapy. The primary goal is to assess the 12-month progression-free survival rate, while secondary objectives include overall survival and safety assessments. Additionally, the study aims to identify potential biomarkers that could predict treatment efficacy.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-80 with advanced, unresectable, or recurrent NSCLC and PD-L1 expression below 1%.

Not a fit: Patients with prior systemic anti-tumor treatment for advanced disease or those with curable stages of lung cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with PD-L1 negative advanced NSCLC.

How similar studies have performed: Other studies have explored similar combinations of immunotherapy and chemotherapy, showing promising results, but this specific approach is novel for PD-L1 negative NSCLC.

Eligibility criteria

Inclusion Criteria:

* Written informed consent must be obtained before implementing any trial-related procedures;
* Aged 18-80 years;
* Expected survival of more than 3 months;
* The investigator confirms the presence of at least one measurable lesion according to RECIST 1.1 criteria;
* Wild-type EGFR/ALK;
* Patients with locally advanced (stage IIIb/IIIc), metastatic, or recurrent (stage IV) NSCLC confirmed by histology or cytology, who are not eligible for curative surgery and cannot undergo definitive radiotherapy/chemotherapy, according to the 8th edition of the TNM staging classification by the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer;
* PD-L1 expression in tumor tissue with Tumor Proportion Score (TPS) \< 1%;
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
* No prior systemic anti-tumor treatment for advanced/metastatic disease; patients who have previously received platinum-based adjuvant chemotherapy/radiotherapy, neoadjuvant chemotherapy/radiotherapy, or curative radiotherapy for advanced disease and experienced disease progression more than 6 months after the last treatment can participate in this study;
* Adequate hematologic function, defined as absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L, platelet count \>= 100 x 10\^9/L, hemoglobin \>= 90 g/L (without transfusion history within 7 days);
* Adequate liver function, defined as total bilirubin level \<= 1.5 times the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels \<= 2.5 times ULN in all patients, or \<= 5 times ULN in patients with liver metastases;
* Adequate renal function, defined as serum creatinine \<= 1.5 times ULN;
* Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) \<= 1.5 times ULN; for subjects receiving anticoagulant therapy, INR/PT should be within the range planned by the anticoagulant;
* Women of childbearing potential must have a negative pregnancy test within 7 days before starting treatment, and must use reliable contraceptive measures (such as intrauterine device, contraceptive pills, and condoms) during the trial and for 30 days after the end of the trial; male subjects of reproductive potential must use condoms for contraception during the trial and for 30 days after the end of the trial;
* Willingness to comply with regular follow-up visits and trial requirements.

Exclusion Criteria:

* Currently participating in interventional clinical research treatment;
* Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or drugs targeting another stimulatory or co-inhibitory T-cell receptor (such as CTLA-4, OX-40, CD137);
* Received traditional Chinese medicine or immunomodulatory drugs (such as thymopeptide, interferon, interleukin, etc.) with anti-tumor indications within 2 weeks prior to the first dose;
* Known allergy to the active ingredient or any excipients of Cadonilimab;
* Active hemoptysis, active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, or peritoneal metastasis requiring clinical intervention;
* Uncontrolled pleural effusion/ascites clinically (patients who do not require drainage of effusion or whose effusion does not increase significantly for 3 days can be included);
* Tumor compression of important organs (such as the esophagus) with accompanying symptoms, compression of the superior vena cava, or invasion of mediastinal large blood vessels, heart, etc.;
* History of severe complications such as severe pulmonary or cardiac disease, with any arterial thrombosis, embolism, or ischemia occurring within 6 months prior to enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack. History of deep vein thrombosis, pulmonary embolism, or any other serious thrombotic events within 3 months prior to enrollment (thrombotic events related to implanted venous infusion ports or catheters, or superficial vein thrombosis are not considered "serious" thrombotic events);
* History of autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis, or glomerulonephritis related to antiphospholipid syndrome; Patients with stable hypothyroidism on replacement therapy with thyroid hormones are eligible to participate in this study; Patients with controlled type 1 diabetes after receiving a stable insulin treatment regimen are eligible to participate in this study;
* Received systemic corticosteroids (\> 10 mg/day of prednisone or equivalent) or other systemic immunosuppressive agents (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] drugs) within 2 weeks prior to randomization; Use of topical, ocular, intra-articular, intranasal, and inhaled corticosteroids is allowed;
* Active systemic infections, including tuberculosis (TB) (clinical diagnosis based on clinical history, physical examination, radiographic findings, and TB testing according to local medical practices), hepatitis B (known positive for hepatitis B surface antigen (HBsAg) with HBV DNA \>= 1,000 cps/mL or its lower limit of reference range), hepatitis C, or human immunodeficiency virus (HIV) (positive for HIV antibody);
* Known presence of mental illness or substance abuse that may affect compliance with trial requirements;
* History of conditions, diseases, treatments, or laboratory abnormalities that may interfere with trial results or hinder the subject's full participation in the study, or as determined by the investigator that participation in the study is not in the best interest of the subject.

Where this trial is running

Shanghai, Shanghai Municipality and 1 other locations

• Shanghai Chest Hospital — Shanghai, Shanghai Municipality, China (NOT_YET_RECRUITING)
• NINGBO No.2 Hospital — Ningbo, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Li Wang

Conditions: NSCLC, PD-L1 negative, PD-1/CTLA-4 bispecific antibody