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

Non Small Cell Lung Cancer Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05284539
• Other study ID #: 20220117
• Status: Recruiting
• Phase: Phase 2
• Start date: April 1, 2022
• Est. completion date: October 10, 2027

Study information

• Verified date: June 2024
• Source: Hunan Province Tumor Hospital
• Contact: Yongchang Zhang, MD
• Phone: +8613873123436
• Email: zhangyongchang[@]csu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 760
• Est. completion date: October 10, 2027
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
China	Hunan Cancer Hospital	Changsha	Hunan

Sponsors (1)

Lead Sponsor	Collaborator
Hunan Province Tumor Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	To assess progression-free survival of patients treated with Immune Checkpoint Inhibitor, Bevacizumab in combination with Chemotherapy according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator, define as first dose to first documented disease progression assessed by investigator or death due to any cause	Time from first subject dose to study completion, or up to 36 month
Secondary	Objective Response Rate (ORR)	To assess PD-1 antibody, Bevacizumab in combination with Chemotherapy overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator, define as the proportion of subjects who have a complete response (CR) or a partial response (PR)	Time from first dose to last dose, or up to 24 month
Secondary	Overall survival (OS)	To assess overall survival, define as first dose to the death of the subject due to any cause	Time from first subject dose to study completion, or up to 36 month
Secondary	Adverse events (AEs) according to CTCAE 5.0	Number of participants with adverse events (AEs) according to CTCAE 5.0	From first dose until 28 days after the last dose, up to 24 month