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

NCT ID: NCT05266846

Last Updated: 2024-05-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-29
• Study Completion Date: 2027-02-16

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.

Conditions

ALK Gene Mutation; Lung Adenocarcinoma; Immunotherapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab plus Bevacizumab and Chemotherapy

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

Group Type: EXPERIMENTAL

Pembrolizumab injection

Intervention Type: DRUG

Pembrolizumab 20mg ivgtt once every 21day Platium based Chemotherapy ivgtt once every 21day Bevacizumab 15mg/kg ivgtt once every 21day

Bevacizumab plus Chemotherapy

Bevacizumab plus Chemotherapy was used for ALK-rearranged NSCLC With Persistent 5'ALK.

Group Type: EXPERIMENTAL

Pembrolizumab injection

Intervention Type: DRUG

Pembrolizumab 20mg ivgtt once every 21day Platium based Chemotherapy ivgtt once every 21day Bevacizumab 15mg/kg ivgtt once every 21day

Interventions

Pembrolizumab injection

Pembrolizumab 20mg ivgtt once every 21day Platium based Chemotherapy ivgtt once every 21day Bevacizumab 15mg/kg ivgtt once every 21day

Intervention Type: DRUG

Other Intervention Names

pemetrexed; Bevacizumab; CISPLATIN

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hunan Province Tumor Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yongchang Zhang

Professor, Deputy Director of Thoracic Oncology Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yongchang C Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Hunan Cancer Hospital

Locations

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yongchang C Zhang, MD

Role: CONTACT

zhangyongchang@csu.edu.cn

+8613873123436 ext. 7+861383123436

Nong C Yang, MD

Role: CONTACT

yangnong0217@163.com

+8613873123436 ext. +8613873123436

Facility Contacts

Yongchang Zhang, MD

Role: primary

zhangyongchang@csu.edu.cn

+86 731 89762323

Nong Yang, MD

Role: backup

yangnong0217@163.com

+86 731 89762321

Other Identifiers

2022017

Identifier Type: -

Identifier Source: org_study_id