Bevacizumab and Chemotherapy With or Without Pembrolizumab in First Line Alectinib Failed ALK-rearranged Advanced Lung Adenocarcinoma Patients With Persistent 5'ALK: A Phase II Randmized Control Trial

Hunan Province Tumor Hospital1 site in 1 country78 target enrollmentMay 29, 2024

Overview

Brief Summary

This is an open-label, multiple centers, two-arms 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.

Detailed Description

This is an open-label, multiple centers, two-arms 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 samples were collected for single-RNA sequencing and DSP to evalutate the TME to predict the efficacy.

Registry

clinicaltrials.gov

Start Date

May 29, 2024

End Date

February 16, 2027

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hunan Province Tumor Hospital

Responsible Party

Principal Investigator

Yongchang Zhang

Professor, Deputy Director of Thoracic Oncology Department

Hunan Province Tumor Hospital

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 .