Lung Cancer
Conditions
Interventions
Phase I group:Cadonilimab combined with local ablative therapy
Phase II experimental group:Cadonilimab combined with local ablative therapy
Phase II control group:Docetaxel
Sponsors
Shanghai Pulmonary Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: (1)Volunteer to participate in the research and sign the informed consent form, subjects to agree to participate in the exploratory biomarker research, including the collection of biological samples (such as plasma, serum, archives, and tumor specimens obtained during the study), and exploratory analysis of biomarkers, which will be used to investigate the correlation between disease activity, drug effects, and clinical outcomes. (2)The researcher judges that he can comply with the research plan; (3)Subjects aged 18-75 years old when they sign the informed consent form, both male and female; (4) Subjects who are diagnosed as non-small cell lung cancer (NSCLC) by histology or cytology and are stage IIIB-IV tumors (according to the 8th edition of the Joint Committee on Cancer Staging Manual); (5)The research center must be able to provide relevant documents about the subject's EGFR mutation, ALK fusion and ROS1 rearrangement status, and they must all be negative. Subjects cannot be randomized into the group before the gene status recorded in the source files of the research center; (6)Subjects must have received only one PD-1/PD-L1 inhibitor (with or without platinum-based chemotherapy) and responded to it (defined as partial or complete response or stable disease for more than 6 months according to RECIST1.1 or irRC standards) before experiencing oligo-progression (=5 lesions and =3 organs). All oligo-progressive lesions should be amenable to complete ablation therapy. ; (7)The subject must have at least one residual lesion identifiable by CT or PET/CT as a target for local thermal ablation and one measurable lesion suitable for repeat accurate measurement (according to RECIST v1.1, the measurable lesion should have a spiral CT scan long diameter =10 mm or lymph nodes with short axis =15 mm). Tumor imaging evaluation must be performed within 28 days before the first use of the drug. The subject must provide historical radiological examination results for comparison, which will be reviewed by the investigator to determine whether there was PD during frontline treatment and to exclude the possibility of pseudoprogression. (8)Tumor tissue specimens archived at the time of diagnosis of advanced or metastatic tumors and within 6 months before the first administration must be provided, as well as archived or freshly obtained after the end of front-line treatment, formalin-fixed, paraffin-embedded Tumor tissue mass after embedding (FFPE). The tissue block provided should be able to cut at least 10 slices for staining and testing (if approved by the sponsors medical supervisor, less than 10 slices can be provided). Fine-needle aspiration biopsy specimens, pleural effusion drainage and centrifugal cell smears, or drill biopsy are not sufficient for biomarker detection. Bone lesions without soft tissue components or decalcified bone tumor specimens are also unacceptable; (9)Able to swallow pills normally. (10) ECOG PS score 0-1 points; (11)The expected survival period >=3 months; (12)Perform all laboratory tests during the screening period in accordance with the requirements of the protocol, and must be performed within 14 days before the first medication. The values of laboratory tests performed by screening must meet the following criteria: a) Hemoglobin (HB) =90 g/L; b) Absolute neutrophil count (ANC) =1.5×109/L; c) White blood cell count (WBC) =4.0×109/L and =15×109/L; d) Platelet count (PLT) =100×109/L; e) Albumin (ALB) =30 g/L; f)
Exclusion criteria
Exclusion criteria: (1) Exclusion criteria for the target disease: 1)Exclude participants who are positive for EGFR mutation, ALK fusion or ROS1 rearrangement. 2)Exclude participants with no measurable lesions . 3)Exclude pregnant or lactating women. 4)Exclude participants with untreated central nervous system (CNS) tumor metastasis, or those with cancerous meningitis or spinal cord compression. However, if the CNS tumor metastasis is limited to the supratentorial and/or cerebellum regions, has been adequately treated and stable clinically (imaging, preferably enhanced MRI or CT), maintained for at least 4 weeks, and the participant's neurological symptoms have recovered to NCI-CTC AE =1 grade for at least 2 weeks before first treatment, they can be enrolled in the study. In addition, participants who use corticosteroid hormones to treat clinical symptoms must receive a stable dose or gradually lower =10 mg/day of prednisone (or equivalent) for at least 2 weeks before participating in the study, otherwise they cannot be included. 5)Exclude participants who can undergo surgical resection or curative radiotherapy. 6)Exclude participants who cannot follow the treatment plan provided by the investigator. (2) Medical history and comorbidities: 1)Exclude participants with any active, known or suspected autoimmune diseases. Participants with stable conditions that do not require systemic immunosuppressive therapy, such as type 1 diabetes, thyroid dysfunction requiring only hormone replacement therapy, skin diseases (e.g., vitiligo, psoriasis, or alopecia) that do not require systemic treatment, or participants who are expected to not relapse without external triggering factors may be eligible for enrollment. 2)Exclude participants who require systemic treatment with corticosteroids (>10 mg/day of prednisone or equivalent) or other immunosuppressive agents within 14 days before the first treatment. In the absence of active autoimmune disease, inhaled or topical use of corticosteroids and adrenal hormone replacement therapy at prednisone-equivalent doses >10 mg/day may be allowed. 3)Exclude participants who have received antitumor vaccines or other anticancer drugs with immunostimulatory effects (interferons, interleukins, thymopentin, immunocyte therapy, etc.) within 1 month before the first treatment. 4)Exclude participants who are currently participating in other clinical trials, or whose first treatment is less than 4 weeks (or 5 half-lives of the study drug) from the end (last dose) of the previous clinical trial. 5)Exclude participants who are expected to require any other form of antitumor therapy during the study (including maintenance therapy for other NSCLC drugs, radiotherapy, and/or surgical resection). 6)Exclude participants who have undergone major surgical procedures within 4 weeks before the first treatment, non-thoracic radiotherapy >30 Gy within 4 weeks before the first treatment, thoracic radiotherapy >30 Gy within 24 weeks before the first treatment, or palliative radiotherapy =30 Gy within 2 weeks before the first treatment and have not recovered from the toxicity and/or complications of these interventions to NCI-CTC AE =1 grade (except for alopecia and fatigue). Palliative radiotherapy for symptom control must be completed at least 2 weeks before the start of treatment with the study drug and additional radiotherapy to the same lesion is not planned. 7)Exclude participants suspected of having interstitial pneumonia, or those who may interfer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 6-month PFS rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate;Progression free survival;Overall survival;safety; | — |
Countries
China
Contacts
Public ContactShengxiang Ren
Shanghai Pulmonary Hospital
Outcome results
None listed