Pembrolizumab Plus Bevacizumab and Chemotherapy for ALK-rearranged NSCLC With Persistent 5'ALK

Study Overview
=================
Brief Summary
-----------------
This is an open-label, multiple center, single-arm phase II study to evaluate the safety and efficacy Pembrolizumab,Bevacizumab in combination with Chemotherapy could improve PFS in Alectinib Failed ALK-rearranged Advanced Lung Adenocarcinoma with Persistent 5'ALK. The eligible patients should have Stage IV Adenocarcinoma ALK-rearranged tested by NGS Perisitent with 5'ALK Failed from first line Alectinib. The patients should meet the physical requirements to receive Pembrolizumab, Bevacizumab with Chemotherapy. All the patients who meet these requirements will be enrolled in this study. The eligible patients will be treated with Pembrolizumab 200 mg intravenously (IV) plus Bevacizumab 15mg/kg+ Pemetrexed 500mg/m2+Carboplatin AUC=4 for up to 4 cycles followed by Pembrolizumab 200mg Q3W+ Bevacizumab 15mg/kg+Pemetrexed 500mg/m2 for up to 31cycles or until disease progression, intolerable toxicity, or physician or participant decision.

Official Title
-----------------
Pembrolizumab Plus Bevacizumab and Chemotherapy in Alectinib Failed ALK-rearranged Advanced Lung Adenocarcinoma Patients With Persistent 5'ALK: An Open Label, Single Arm, Phase II Trial

Conditions
-----------------
ALK Gene Mutation, Lung Adenocarcinoma, Immunotherapy

Intervention / Treatment
-----------------
* Drug: Pembrolizumab Combined With Bevacizumab and Chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years of age on day of signing informed consent. Stage IV ALK-rearranged Lung Adenocarcinoma Persistent with 5'ALK Failed from first line Alectinib Have at least 1 lesion that meets the criteria for being measurable, as defined by RECIST 1.1, and is appropriate for selection as a target lesion, as determined by local site investigator radiology review. Lesions that appear measurable, but have undergone palliative irradiation, cannot be target lesions ④20 FFPE sliders prepared,Subjects who do not have histology samples (defined as core or excisional biopsy, or resections) will need to undergo a new biopsy to provide a tissue sample ⑤Eastern Cooperative Oncology Group performance status 0 or 1 Life expectancy ≥3 months Adequate hematologic and end organ function Exclusion Criteria: Cancer-Specific Exclusions: ①Active or untreated central nervous system metastases ②Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome General Medical Exclusions: Pregnant or lactating women. Has active autoimmune disease that has required systemic treatment in the past 2 years. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. Positive test for human immunodeficiency virus. ⑤Active hepatitis B or hepatitis C. ⑥Severe infection within 4 weeks prior to randomization . ⑦Significant cardiovascular disease. ⑧Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures. ⑨Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment for another health-related problem. Exclusion Criteria Related to Medications: Prior treatment with anti-programmed death-1, anti-PD-L1 therapeutic antibodies，and anti-VEGF agents.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab plus Bevacizumab and Chemotherapy<br>Pembrolizumab Plus Bevacizumab and Chemotherapy was used for ALK-rearranged NSCLC With Persistent 5'ALK. | Drug: Pembrolizumab Combined With Bevacizumab and Chemotherapy<br>* Pembrolizumab + Bevacizumab + Chemotherapy<br>* Other names: PCBC or IMPOWER 150;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Defined as the time from the beginning of treatment to the first imaging disease progression or death (whichever occurs first) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Defined as the proportion of subjects in complete remission (CR) and partial remission (PR) to the total subjects | 2 years | 
| DCR | Defined as the proportion of subjects with complete remission (CR), partial remission (PR) and stable disease (SD) to the total subjects | 2 years |