Combining chemotherapy with immune therapy for specific lung cancer mutations

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

This study is testing if combining chemotherapy with immune therapy can help people with specific types of lung cancer who haven't responded to other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 760 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hunan Province Tumor Hospital (Academic / other)
• Drugs / interventions: radiation, Chemotherapy, Osimertinib, Alectinib, Lorlatinib, Ceritinib, Ensartinib, Brigatinib, Crizotinib, Entrectinib
• Locations: 1 site (Changsha, Hunan)
• Trial ID: NCT05284539 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the efficacy and safety of platinum-based chemotherapy combined with immune checkpoint inhibitors in patients with EGFR, ALK, or ROS1 mutant non-small cell lung cancer (NSCLC) who have failed first-line treatments. The study is divided into three cohorts based on the specific mutations: EGFR, ALK, and ROS1. Participants will undergo treatment with drugs such as Pemetrexed, Cisplatin, Bevacizumab, and Pembrolizumab, and their safety and efficacy will be closely monitored. Additionally, tissue and blood samples will be collected for advanced analysis of the tumor microenvironment.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced NSCLC harboring EGFR, ALK, or ROS1 mutations who have progressed after first-line therapy.

Not a fit: Patients with active central nervous system metastases or other malignancies, as well as those with a history of autoimmune diseases, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new effective treatment option for patients with specific mutations in lung cancer who have not responded to standard therapies.

How similar studies have performed: Other studies have shown promising results with similar combinations of chemotherapy and immune checkpoint inhibitors in lung cancer, indicating potential for success in this approach.

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.

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.

Where this trial is running

Changsha, Hunan

• Hunan Cancer Hospital — Changsha, Hunan, China (Recruiting)

Study contacts

• Principal investigator: Yongchang Zhang, MD — Hunan Cancer Hospital
• Study coordinator: Yongchang Zhang, MD

Conditions Non Small Cell Lung Cancer; EGFR; ALK; ROS1; PD-1 Blockade