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

NCT ID: NCT05284539

Last Updated: 2024-06-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 760 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-01
• Study Completion Date: 2027-10-10

Brief Summary

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.

Detailed Description

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.

Conditions

Non Small Cell Lung Cancer

Study Design

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

Study Groups

Arm A: EGFR mutant Group

EGFR mutant Group.

Group Type: EXPERIMENTAL

Pemetrexed, Cisplatin, Bevacizumab Plus Pembrolizumab

Intervention Type: DRUG

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.

Arm B: ALK fusion Group

ALK fusion Group.

Group Type: EXPERIMENTAL

Pemetrexed, Cisplatin, Bevacizumab Plus Pembrolizumab

Intervention Type: DRUG

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.

Cohort C: ROS1 fusion Group.

ROS1 fusion Group.

Group Type: EXPERIMENTAL

Pemetrexed, Cisplatin, Bevacizumab Plus Pembrolizumab

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Pemetrexed; Bevacizumab; Pembrolizumab; Atezolizumab

Eligibility Criteria

Inclusion Criteria

1. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.

2. Age ≥ 18 years.

3. Histologically or cytologically confirmed, Stage IV NSCLC.

4. EGFR/ALK/ROS1-sensitive mutations confirmed by an accredited local laboratory, progressed from first line systematic therapy.

5. ECOG 0-1.

6. Predicted survival ≥ 12 weeks.

7. Adequate bone marrow hematopoiesis and organ function

8. Presence of measurable lesions according to RECIST 1.1.

Exclusion Criteria

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.

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

• 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

Head of Medical Oncology, Director of Early Clinical Trial Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yongchang Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Hunan Cancer Hospital

Locations

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yongchang Zhang, MD

Role: CONTACT

zhangyongchang@csu.edu.cn

+8613873123436 ext. 7+861383123436

Nong 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

20220117

Identifier Type: -

Identifier Source: org_study_id