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

Hunan Province Tumor Hospital

Status and phase: Enrolling; Phase 2

Conditions: Non Small Cell Lung Cancer

Treatments: Drug: Pemetrexed, Cisplatin, Bevacizumab Plus Pembrolizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT05284539

20220117

Details and patient eligibility

About

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.

Full 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.

Enrollment: 760 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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760 participants in 3 patient groups

Arm A: EGFR mutant Group

Experimental group

Description:

EGFR mutant Group.

Treatment:

Drug: Pemetrexed, Cisplatin, Bevacizumab Plus Pembrolizumab

Arm B: ALK fusion Group

Experimental group

Description:

ALK fusion Group.

Treatment:

Drug: Pemetrexed, Cisplatin, Bevacizumab Plus Pembrolizumab

Cohort C: ROS1 fusion Group.

Experimental group

Description:

ROS1 fusion Group.

Treatment:

Drug: Pemetrexed, Cisplatin, Bevacizumab Plus Pembrolizumab