Neoadjuvant Sunvozertinib in Stage II-IIIB Non-small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutation.

A Phase II, Single-arm, Single-center Study of Neoadjuvant Sunvozertinib for Stage II-IIIB Non-small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations.

To assess the efficacy and safety of sunvozertinib as neoadjuvant therapy in patients with stage II-IIIB non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins).

Study Overview

• Status: Active, not recruiting
• Conditions: Non Small Cell Lung Cancer; Potentially Resectable EGFR Exon 20 Insertion Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Sunvozertinib

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Shanghai Pulmonary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. The patient must understand the trial requirements and contents, and provide written informed consent.

  2.Age ≥ 18 years. 3.Histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC). Assessed as resectable Stage II-III disease (per the American Joint Committee on Cancer (AJCC) 8th edition).

  4.Confirmed EGFR exon 20 insertion mutation by a validated test. 5.No evidence of disease progression within the past two weeks prior to signing informed consent and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

  6.Adequate hematological and organ function, as defined by: 7.Hematological: Absolute Neutrophil Count (ANC) ≥ 1.5 × 10^9/L Platelet count ≥ 100 × 10^9/L Hemoglobin ≥ 9 g/dL

Hepatic:

Total bilirubin ≤ 1.5 × Upper Limit of Normal (ULN); for patients with Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases, total bilirubin ≤ 3 × ULN.

Alanine Aminotransferase (ALT) ≤ 2.5 × ULN and Aspartate Aminotransferase (AST) ≤ 2.5 × ULN in the absence of liver metastases; or ALT and AST ≤ 5 × ULN for patients with liver metastases.

Renal:

Serum creatinine ≤ 1.5 × ULN, AND Calculated or measured creatinine clearance ≥ 60 mL/min (using the Cockcroft-Gault formula).

8.Male patients with female partners of childbearing potential must agree to use a highly effective barrier method of contraception (e.g., condom) during the trial intervention period and for 6 months after the last dose. Male patients must refrain from donating sperm during this same period.

9.Female patients must agree to use contraception from the time of screening until 6 weeks after the last dose, must not be breastfeeding, and must have a negative pregnancy test (serum or urine beta-human chorionic gonadotropin, β-hCG) at screening.

Exclusion Criteria:

• 1.Prior systemic anti-tumor therapy, including chemotherapy, targeted therapy, immunotherapy, and investigational agents from other clinical trials.

  2.History of other malignancies within the past 2 years (except for adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix).

  3.History of stroke or intracranial hemorrhage within 6 months prior to the first dose.

  4.Severe or uncontrolled systemic diseases/active infection. 5.Any severe or poorly controlled systemic disease, in the investigator's judgment, including but not limited to the following cardiac conditions or abnormalities: QT interval corrected using Fridericia's formula (QTcF) > 470 msec at rest on electrocardiogram (ECG).

Any clinically significant abnormalities in cardiac rhythm, conduction, or morphology at rest on ECG, such as complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, PR interval > 250 msec.

Any factors that increase the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death in a first-degree relative under 40 years of age, or any other known condition associated with prolonged QT interval.

Presence of atrial fibrillation (except for drug-induced atrial fibrillation which has resolved after discontinuation of the causative agent).

Myocardial infarction ≤ 6 months prior to the first dose, New York Heart Association (NYHA) Class II or higher congestive heart failure, or poorly controlled arrhythmia despite medical treatment.

6.History of interstitial lung disease (ILD), drug-induced ILD, or any evidence of ILD on imaging at screening.

7.Refractory nausea and vomiting, chronic gastrointestinal diseases, or significant bowel resection that would preclude adequate absorption of Sunvozertinib.

8.Women who are breastfeeding or pregnant. 9.Known hypersensitivity to the active ingredient or any excipients of Sunvozertinib.

10.Patients who, in the judgment of the investigator, are unsuitable for participation in this clinical trial or are unlikely to comply with the study procedures and requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sunvozertinib 300 mg orally, once daily	Drug: Sunvozertinib; Participants will receive oral administration of sunvozertinib 300 mg QD, with each treatment cycle defined as 28 days, until meeting any treatment discontinuation criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR is defined according to the RECIST v1.1 criteria.	up to 30 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Major pathologic response (MPR) rate	Up to 30 months
Pathological complete response (pCR) rate	Up to 30 months
Event-free suvival (EFS)	Up to 60 months
Overall suvival (OS)	Up to 60 months
R0 resection rate	Up to 30 months
N2 downstaging rate after neoadjuvant treatment	Up to 30 months
Treatment-related adverse event (TRAE)	Up to 30 months
Incidence of treatment discontinuation due to AE/SAE	Up to 30 months

Collaborators and Investigators

• Sponsor: Shanghai Pulmonary Hospital, Shanghai, China

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2024
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: November 28, 2025
• First Submitted That Met QC Criteria: November 28, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: November 28, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: neoadjuvant; Sunvozertinib; Non-small Cell Lung Cancer stage II-IIIB; EGFR Exon 20 insertion
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: LungMate-035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The researchers will consider whether IPD is available to other researchers only after the paper is published.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No