Efficacy of Platinum-based Chemotherapy Plus Immune Checkpoint Inhibitors for EGFR/ALK/ROS1 Mutant Lung Cancer

Официальное название

Efficacy of Platinum-based Chemotherapy With or Without Immune Checkpoint Inhibitors in Patients With EGFR/ALK/ROS1 Sensitive Mutated NSCLC Who Progressed From Previous Tyrosine Kinase Inhibitors (TKI) Therapy

Обзор

The investigators want to evaluate the Efficay and Safety of Platinum-based Chemotherapy with or without immune checkpoint inhibitors for EGFR/ALK/ROS1 Positive NSCLC who Failed from First-Line Standard Treatment.

Подробное описание

The investigators want to evaluate the Efficacy and Safety of Platinum-based Chemotherapy with or without immune checkpoint inhibitors for EGFR/ALK/ROS1 Positive NSCLC who Failed from First-Line Standard Treatment.

This study will be divided into three cohorts. Cohort A for EGFR mutation NSCLC, Patient with NGS identified EGFR sensitive mutation NSCLC who failed from first line Osimertinib will be included.

Cohort B for ALK fusion NSCLC, Patient with NGS identified ALK fusion NSCLC who failed from first line Alectinib/Lorlatinib/Ceritinib/Ensartinib/Brigatinib will be included. All the patients will be divided two group,3'ALK and 3'ALK with retention of 5'ALK.

Cohort C for ROS1 fusion NSCLC, Patient with NGS identified ROS1 fusion NSCLC who failed from first line Crizotinib/Entrectinib/Ensartinib/Brigatinib will be included.

The investigators will collect the safety and efficacy data for all the patients.

The tissue and blood samples will be collected under the permission of the participate.

Single cell sequencing, DSP, RNA-seq and IHC will be performed to evaluate the TME.

Вмешательства

• Препарат Pemetrexed, Cisplatin, Bevacizumab Plus Pembrolizumab
  Pemetrexed, 500mg/m2, ivgtt, every 21 days. Bevacizumab 15mg/kg, ivgtt, every 21 days. Pembrolizumab, 200mg ivgtt, every 21 days. Atezolizumab, 1200mg, ivgtt, every 21 days.

Первичные конечные точки

• Progression-free survival (PFS) [Срок оценки: Time from first subject dose to study completion, or up to 36 month]

Вторичные конечные точки (3)

• Objective Response Rate (ORR) [Срок оценки: Time from first dose to last dose, or up to 24 month]
• Overall survival (OS) [Срок оценки: Time from first subject dose to study completion, or up to 36 month]
• Adverse events (AEs) according to CTCAE 5.0 [Срок оценки: From first dose until 28 days after the last dose, up to 24 month]

Критерии участия

Критерии включения

• Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
• Age ≥ 18 years.
• Histologically or cytologically confirmed, Stage IV NSCLC.
• EGFR/ALK/ROS1-sensitive mutations confirmed by an accredited local laboratory, progressed from first line systematic therapy.
• ECOG 0-1.
• Predicted survival ≥ 12 weeks.
• Adequate bone marrow hematopoiesis and organ function
• Presence of measurable lesions according to RECIST 1.1.

Критерии исключения

Cancer-Specific Exclusions:

• Active or untreated central nervous system metastases.
• Malignancies 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.
• History of autoimmune disease.
• 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.
• Active hepatitis B or hepatitis C.
• Severe infection within 4 weeks prior to randomization.
• Significant cardiovascular disease.
• Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures.

Exclusion Criteria Related to Medications:

• Prior treatment with cluster of differentiation 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1, and anti-PD-L1 therapeutic antibodies.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Hunan Cancer Hospital — Чанша

Идентификаторы

NCT: NCT05284539 · 20220117

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗