Toripalimab in Combination With Chemotherapy and Antiangiogenic Agents in Patients With Non-Small Cell Lung Cancer After Failure of Immunotherapy (PD-1/L1 Inhibitors)

Study Overview
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Brief Summary
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This is a phase II, single arm, open-label, single-center study to evaluate the efficacy and safety of Toripalimab combined with Chemotherapy and Antiangiogenic Agents in patients with Non-Small Cell Lung Cancer After Failure of Immunotherapy (PD-1/L1 inhibitors)

Official Title
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Toripalimab in Combination With Chemotherapy and Antiangiogenic Agents in Patients With Non Small Cell Lung Cancer After Failure of Immunotherapy (PD-1/L1 Inhibitors): a Prospective, Single-arm, Phase II Trial

Conditions
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Non Small Cell Lung Cancer Recurrent

Intervention / Treatment
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* Drug: Toripalimab, Anlotinib and Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients voluntarily participate in this study, signed and dated informed consent with good compliance and follow-up; Diagnosed as locally advanced and / or metastatic non-small cell lung adenocarcinoma (NSCLC) by cytology or histology; First-line PD-1/PD-L1 inhibitors treatment failure; Provide detectable specimens (tissue or blood) for genotyping before enrollment, and the patients should be with negative EGFR and ALK gene test results; Had at least one measurable lesion according to RECIST 1.1 criteria Anticipated overall survival more than 3 months; ECOG (Eastern Cooperative Oncology Group) scale 0-2; Normal organ function and bone marrow function; Resistant to first-line immune checkpoint inhibitor therapy and discontinued for more than 4 weeks; Women of childbearing age must have taken reliable contraceptive measures and performed a pregnancy test (serum or urine) within 7 days prior to enrollment, and the results were negative, and were willing to use appropriate methods during the trial and 4 weeks after the last administration of the test drug. Exclusion Criteria: Patients with small cell lung cancer (including small cell carcinoma and non-small cell carcinoma mixed lung cancer) ; Patients who have previously permanently discontinued immunotherapy due to immune-related serious adverse reactions; Patients who previously treated with antiangiogenic agents; A history of other malignancies within 5 years prior to inclusion, except for cervical carcinoma in situ, basal or squamous cell skin cancer, localized prostate cancer treated with radical surgery, and ductal carcinoma in situ treated with radical surgery; Active, known or suspected autoimmune disease; Active or chronic hepatitis C or/and hepatitis B infection; History of interstitial lung disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Toripalimab, Chemotherapy and Antiangiogenic Agents<br> | Drug: Toripalimab, Anlotinib and Chemotherapy<br>* Combination therapy: Toripalimab 240mg will be intravenously administered on Day 1, Q3W; anlotinib: 12 mg qd d1-d14, d15-d21 discontinued, Q3W; investigator selected chemotherapy regimen (paclitaxel, pemetrexed or gemcitabine and other chemotherapeutic drugs which were not administered in the first-line therapy) for a total of 4 cycles. Maintenance therapy: After combination therapy, Patients who achieved complete response（CR）, partial response (PR), or stable disease (SD) were administered with toripalimab plus anlotinib as maintenance therapy. until disease progression or intolerable toxicity, treatment for 2 years, investigator decision, withdrawal of consent, or death.<br>* Other names: JS001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress free survival | Progress free survival is defined as the time from first dose of study treatment until the first date of either disease progression or death due to any cause. | until Progressive Disease (PD) or death (up to 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective response rate is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy. | each 21 days up to intolerance the toxicity or PD (up to 24 months) | 
| Overall Survival | Overall survival is defined as the time until death due to any cause. | from first dose of study treatment until death (up to 24 months) | 
| Disease Control Rate | Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1. | each 21 days up to intolerance the toxicity or PD (up to 24 months) |