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This phase II trial studies how well cadonilimab combined with Bevacizumab and docetaxel work in treating patients with non-squamous and stage IV non-small cell lung cancer. Cadonilimab, a PD-1/CTLA-4 bispecific antibody, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab can regulate tumor microenvironment. Docetaxel was used in standard of care chemotherapy for non-small cell lung cancer, work to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving cadonilimab, bevacizumab and docetaxel together may work better in treating patients with non-squamous non-small lung cancer compared to standard of care.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A (cadonilimab,bevacizumab,docetaxel ) | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cadonilimab,bevacizumab,docetaxel | Drug | Patients receive Cadonilimab IV over 90 minutes on day 1. Patients also receive bevacizumab 7.5mg/kg IV on day 1 and docetaxel 60-75 mg/m2 IV over 60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
| Measure | Description | Time Frame |
|---|---|---|
| 6-month progression-free survival | Will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be reported and its 95% confidence intervals will be estimated using the Clopper-Pearson method. PFS rates of two patient groups stratified by binary biomarker (PD-L1 and KRAS status), respectively will be estimated with the Kaplan-Meier method and compared using the log-rank test, respectively. Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of PD-L1 and KRAS status on the patients' PFS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models. | up to 6 months |
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Inclusion Criteria:
Age≥18 years old
Locally advanced (stage IIIB/IIIC) that cannot be resected by radical surgery and cannot accept radical synchronous/sequential radiotherapy and chemotherapy and metastatic (stage IV) non-squamous NSCLC confirmed by histology or cytology
Patients must have progressed on at most a PD-1/L1 inhibitor and a platinum-based chemotherapy (combined or sequential, regardless of sequence), and at least two cycles of PD-1/L1 inhibitor (combined or non-combined chemotherapy) with clinical benefits (PFS ≥ 3 months)
Patients must not have EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, and ROS 1 gene rearrangement, and BRAF V600E mutation.
Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Life expectancy > 12 weeks as determined by the investigator
Patients must have at least one measurable lesion (as defined by RECIST v1.1), which is suitable for repeated and accurate measurement
Absolute neutrophil count (ANC) ≥ 1500/uL (collected within 10 days prior to the start of study treatment)
Platelets ≥ 100 000/uL (collected within 10 days prior to the start of study treatment)
Hemoglobin ≥ 9.0 g/dL (collected within 10 days prior to the start of study treatment)
Creatinine clearance [CrCl]) ≥ 50 mL/min(Creatinine clearance (CrCl) should be calculated per institutional standard)
Total bilirubin ≤ 1.5 x ULN (collected within 10 days prior to the start of study treatment)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x ULN (≤ 5 x ULN for participants with liver metastases) (collected within 10 days prior to the start of study treatment
Serum albumin(ALB)≥28 g/L
International standardized ratio (INR) and activated partial thrombin time (APTT) ≤ 1.5 × ULN
Left ventricular ejection fraction (LVEF) ≥ 50%
A male participant must agree to use a contraception during the treatment period plus an additional 120 days after the last dose of study treatment and refrain from donating sperm during this period
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xifang Liu | Contact | 15901246224 | xifang.liu@easytrial.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chinese Academy of Medical Sciences and Peking Union Medical College | Recruiting | Beijing | Beijing Municipality | 100000 | China |
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| ID | Term |
|---|---|
| D008175 | Lung Neoplasms |
| ID | Term |
|---|---|
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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|
| D008171 |
| Lung Diseases |
| D012140 | Respiratory Tract Diseases |