Unresectable Lung Non-Small Cell Carcinoma
Conditions
Keywords
Unresectable NSCLC, Serplulimab, Conversion treatment
Brief summary
This is a phase II, single-arm study to evaluate the efficacy and safety of Serplulimab plus chemotherapy as conversion treatment in patients with stage IIIB-IVA oligometastatic non-small cell lung cancer.
Detailed description
This single-arm, open-label, prospective phase II clinical trial was designed to evaluate the efficacy and safety of Serplulimab plus chemotherapy as conversion treatment in patients with stage IIIB-IVA oligometastatic non-small cell lung cancer. The primary endpoints were the rate of NSCLC converting to resectable tumors and the 1-year progression-free survival (PFS) rate.The secondary endpoints included the rates of R0 resection, major pathological response (MPR) and pathological complete response (pCR), overall survival (OS) and PFS. Multi-omics analysis will be performed to identify potential biomarkers for treatment response.
Interventions
PROCEDUREserplulimab plus chemotherapy as conversion treatment
Patients with unresectable NSCLC will receive serplulimab plus chemotherapy as conversion treatment, and then curative pneumonectomy will be provided for patients who are suitable for primary tumor resection. Locoregional ablative treatments will be performed for metastatic lesions.
Sponsors
Zhejiang University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients should voluntarily join this study and sign the informed consent form 2. NSCLC patients diagnosed by cytology or histology and not previously receiving anti-tumor treatments (including systemic treatments, local treatments .etc) 3. Patients with IIIB - IVA oligometastatic NSCLC : (a) IIIB - IIIC stage (T1-4N2-3): patients are not suitable or refuse to receive upfront surgical resection or radiotherapy; (b) oligometastatic stage IV (T1-3N0-2): radical resection/radiotherapy is feasible for metastatic lesions (the number of metastases being up to 3, and the maximum diameter of metastases being up to 2cm) 4. After evaluation by MDT, upfront surgical resection is not the preferred treatment, but after induction systemic treatments, radical resection of the primary tumor is feasible, and radical resection/radiotherapy is feasible for extrathoracic metastases (if any) 5. Age from 18 to 75 years old, both male and female 6. ECOG score 0-1 7. According to the RECIST v1.1 , patients should have at least one measurable lesion 8. For suspicious mediastinal lymph nodes (including pathological enlargement or PET-CT indicating malignancy, etc.), further sampling is required for pathological diagnosis by EUBS, thoracoscopy, or mediastinoscopy 9. According clinical evaluation, the lung function of patients (such as FVC, FEV1, TLC, FRC, DLco, etc.) should be sufficient for pneumonectomy 10. The function of important organs should meet the following requirements: absolute count of neutrophils ≥ 1.5 × 109/L； Platelets ≥ 100 × 109/L； Hemoglobin ≥ 90g/L; Serum albumin ≥ 35g/L; Thyroid hormone (TSH) ≤ 1 × ULN； Serum bilirubin ≤ 1.5 × ULN； ALT and AST ≤ 3 × ULN； International standardized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 × ULN； Serum creatinine ≤ 1.5 × ULN 11. Female patients at childbearing age are required to use contraceptive measures; for male patients whose partners are women at childbearing age, effective methods of contraception should be used during the trial period
Exclusion criteria
Patients who meet any of the following conditions will not be enrolled in this study: 1. NSCLC patients have sensitive EGFR mutation, EML4-ALK fusion or other forms of ALK gene changes 2. Patients have previously received immune checkpoint inhibitors such as PD-1/ PD-L1/CTLA4 antibody 3. Patients with other primary malignancies within the past 3 years (excluding cured skin basal cell carcinoma and cervical carcinoma in situ) 4. Patients with active hepatitis B/C 5. Patients with any active autoimmune diseases or a history of autoimmune diseases 6. Patients who are using immunosuppressive agents or require systemic hormone therapy 7. Patients with hypertension but without good control even through antihypertensive medication treatment ; patients with clinical symptoms or diseases related to unsatisfying cardiac function 8. Patients with abnormal coagulation function (INR\>2.0, PT\>16s) 9. Arterial/venous thrombotic events occurred before screening within 6 months 10. Patients with active infection 11. Patients with congenital or acquired immune dysfunction (such as HIV infection) 12. According to the judgment of the researchers, patients have other factors that may affect the results of the research or cause the research to be terminated
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the rate of NSCLC converting to resectable tumors | up to 16 weeks | the proportion of unresectable NSCLC patients who are converted to being suitable for radical pneumonectomy after 3-4 cycles serplulimab plus chemotherapy |
| the 1-year progression-free survival (PFS) rate | up to one year | the proportion of patients who are progression-free after pneumonectomy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | up to five years | The duration from the date of initial treatment to the date of death due to any cause |
| the rate of R0 resection | immediately after the surgery | the proportion of R0 resection in patients who receive pneumonectomy |
| the rate of pathological complete response (pCR) | up to 16 weeks | the proportion of patients who achieve pCR among those receiving pneumonectomy |
| the rate of major pathological response (MPR) | up to 16 weeks | the proportion of patients who achieve MRP among those receiving pneumonectomy |
| Progression-free survival (PFS) | up to five years | The duration from the date of initial treatment to the date of disease progression or death due to any cause |
Countries
China
Contacts
Primary ContactPeng Zhao, MD
Backup ContactJian Hu, MD
Outcome results
None listed