Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations.

NCT06563999 | Recruiting Phase 2 DMC

• 1 other identifier: GASTO-10117
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This umbrella trial directed by next generation sequencing (NGS) includes patients with treatment-naive unresectable stage III non-small-cell lung cancer (NSCLC). The aim of the umbrella study is to evaluate the efficacy of induction NGS-directed targeted therapies followed by surgery for stage III NSCLC patients whose tumor harbors a rare mutation.

Conditions

Lung Cancer Stage III; Mutation

Keywords

stage III NSCLC; rare mutations; umbrella trial; neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Resectability rate

  Baseline to 6 months

Secondary Outcomes (4)

• Adverse Events

  Baseline to 24 months

• Two-year disease-free survival

  2 years after the last patient is randomized

• Two-year overall survival

  2 years after the last patient is randomized

• Number of participants with perioperative complications

  Baseline to 12 months

Study Arms (9)

Treatment 1-Sunvozertinib

EXPERIMENTAL

Patients with EGFR exon20ins mutation receive Sunvozertinib 300 mg orally once a day, 28 days as one cycle for 3 cycle.

Drug: Sunvozertinib

Treatment 2-Crizotinib

EXPERIMENTAL

Patients with ROS1 fusion mutation receive Crizotinib 250mg orally once a day, 28 days as one cycle for 3 cycle.

Drug: Crizotinib

Treatment 3-Pralsetinib

EXPERIMENTAL

Patients with RET fusion mutation receive Pralsetinib 400mg orally once a day, 28 days as one cycle for 3 cycle.

Drug: Pralsetinib

Treatment 4-Larotrectinib

EXPERIMENTAL

Patients with NTRK fusion mutation receive Larotrectinib 100 mg orally twice daily, 28 days as one cycle for 3 cycle.

Drug: Larotrectinib

Treatment 5-Savolitinib

EXPERIMENTAL

Patients with MET 14 exon mutation receive Savolitinib 600 mg or 400 mg (weight \<50 kg) orally once a day, 28 days as one cycle for 3 cycle.

Drug: Savolitinib

Treatment 6-Pyrotinib

EXPERIMENTAL

Patients with HER2 mutation receive Pyrotinib 400 mg orally once a day, 28 days as one cycle for 3 cycle.

Drug: Pyrotinib

Treatment 7-Dabrafenib+Trametinib

EXPERIMENTAL

Patients with BRAF V600E mutation receive Dabrafenib plus Trametinib, 28 days as one cycle for 3 cycle.

Drug: Dabrafenib+Trametinib

Treatment 8-Glecirasib

EXPERIMENTAL

Patients with KRAS G12C mutation receive Glecirasib 800 mg daily orally, 28 days as one cycle for 3 cycle.

Drug: Glecirasib

Treatment 9-Ensartinib

EXPERIMENTAL

Patients with ALK fusion mutation receive Ensartinib 225 mg daily orally, 28 days as one cycle for 3 cycle.

Drug: Ensartinib

Interventions

Sunvozertinib DRUG

300 mg orally once a day, 28 days as one cycle.

Also known as: DZD9008

Treatment 1-Sunvozertinib

Crizotinib DRUG

300 mg orally once a day, 28 days as one cycle.

Also known as: Xalkori

Treatment 2-Crizotinib

Pralsetinib DRUG

400 mg orally once a day, 28 days as one cycle.

Also known as: GAVRETO

Treatment 3-Pralsetinib

Larotrectinib DRUG

100 mg orally twice daily, 28 days as one cycle.

Also known as: VITRAKVI

Treatment 4-Larotrectinib

Savolitinib DRUG

600 mg or 400 mg (weight \<50 kg) orally once a day, 28 days as one cycle.

Also known as: ORPATHYS

Treatment 5-Savolitinib

Pyrotinib DRUG

400 mg orally once a day, 28 days as one cycle.

Also known as: SHR1258

Treatment 6-Pyrotinib

Dabrafenib+Trametinib DRUG

Dabrafenib 150 mg orally twice daily, 28 days as one cycle. Trametinib 150 mg orally twice daily, 28 days as one cycle.

Treatment 7-Dabrafenib+Trametinib

Glecirasib DRUG

800 mg daily orally, 28 days as one cycle.

Also known as: JAB-21822

Treatment 8-Glecirasib

Ensartinib DRUG

225 mg daily orally, 28 days as one cycle.

Also known as: X-396

Treatment 9-Ensartinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Crizotinib; pralsetinib; larotrectinib; 1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine; pyrotinib; ensartinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Study Officials

• Si-Yu Wang, MD

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Si-Yu Wang, MD

CONTACT

+86 20 87343439; wangsy@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 19, 2024
• First Posted: August 21, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2029
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

CN (1)