Targeted therapy for patients with unresectable stage III lung cancer and rare mutations

Neoadjuvant Umbrella Trial Directed by Next Generation Sequencing for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations (Without EGFR Sensitizing Mutations)

This study is testing if targeted therapies for rare mutations can help patients with advanced lung cancer who can't have surgery and haven't been treated before.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06563999 on ClinicalTrials.gov

What this trial studies

This umbrella trial utilizes next generation sequencing (NGS) to identify patients with treatment-naive unresectable stage III non-small-cell lung cancer (NSCLC) that harbor rare mutations. The study aims to evaluate the efficacy of NGS-directed targeted therapies, such as Sunvozertinib and Crizotinib, followed by surgical intervention. Given the challenges posed by the heterogeneity of stage III NSCLC, this approach seeks to provide a tailored treatment strategy for patients who may not benefit from conventional therapies. The trial focuses on patients whose tumors do not have common EGFR mutations, thereby exploring alternative therapeutic avenues.

Who should consider this trial

Good fit: Ideal candidates include treatment-naive patients aged 18-75 with unresectable stage III NSCLC and specific rare mutations identified through NGS.

Not a fit: Patients with common EGFR mutations or those who do not meet the inclusion criteria for rare mutations may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could provide a new targeted treatment option for patients with rare mutations in stage III NSCLC, potentially improving their outcomes.

How similar studies have performed: While targeted therapies for NSCLC have shown promise, this specific approach focusing on rare mutations is relatively novel and has not been extensively tested in previous studies.

Eligibility criteria

Inclusion Criteria:

* Subjects must have treatment-naive unresectable stage III NSCLC according to the AJCC 8th edition staging;
* Squamous or non-squamous NSCLC histology;
* Subjects should have a rare mutation based on NGS, including mutations of EGFR exon20ins, ROS1 fusion, RET fusion, NTRK fusion, MET 14 exon, HER2, BRAF V600E, KRAS G12C, and ALK fusion.
* Subjects should be without EGFR exon 19 deletions or exon 21 L858R activating mutation;
* Male and female, aged 18-75 years;
* Blood and specimens before and after treatment must be provided;
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
* Adequate hematological function: Absolute neutrophil count (ANC) ≥2.0 x 109/L, and Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level);
* Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN;
* Adequate renal function: Serum creatinine ≤ 1.25 x ULN, or ≥ 60 ml/min;
* Female subjects should not be pregnant or breast-feeding;
* Written informed consent provided. Being willing and able to comply with the visits, treatment plan, laboratory examinations and other study procedures scheduled in the study.

Exclusion Criteria:

* Not unresectable stage III disease according to the investigator;
* Subjects with known EGFR sensitive mutations;
* Previous treatment with systemic antitumor therapy for NSCLC;
* Eye inflammation or eye infection not fully treated or conditions predisposing the subject to this.
* History of another malignancy in the last 5 years with the exception of the following: other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.
* Evidence of clinically active interstitial lung disease;
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
* Inability to comply with protocol or study procedures;
* Any unstable systemic disease (including active infection, active tuberculosis uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease);
* A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study and may confuse the study results;
* Women who are pregnant or nursing.
* Ingredients mixed with small cell lung cancer patients.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Si-Yu Wang, MD — Sun Yat-Sen University Cancer Center
• Study coordinator: Si-Yu Wang, MD

Conditions: Lung Cancer Stage III, Mutation, stage III NSCLC, rare mutations, umbrella trial, neoadjuvant