Disitamab Vedotin Combined Therapy for Locally Advanced or Metastatic NSCLC Patients With HER2 Alterations

Disitamab Vedotin Combined Therapy for Locally Advanced or Metastatic NSCLC With HER2 Alterations, a Phase II Study

Disitamab Vedotin combined therapy locally advanced or metastatic NSCLC Patients with HER2 Alterations.

This study will explore the treatment of locally advanced or metastatic non-small cell lung cancer with HER2 mutation, amplification, or HER2 mutation (mutation, amplification, protein over-expression) using Disitamab Vedotin（RC48） combined with Tislelizumab or third-generation EGFR-TKI Furmonertinib, in the aim of providing new treatment strategies for lung cancer patients with HER2 pathway activation.

Inclusion Criteria:

1. Age: 18 (inclusive) or above, regardless of gender.

2. Histologically or cytologically confirmed locally advanced or metastatic NSCLC, not suitable for radical surgery or radiotherapy (TNM 8th Edition).".

3. Biomarker:

   • Arm 1: HER2 alterations, no other driver gene mutations；
   • Arm 2: EGFR mutations accompanied by HER2 alterations;
   • Arm 3: HER2 gene mutations, no other driver gene alterations;

4. Number of treatment lines:

   • Arm 1-2: patients who have not previously received systemic treatment for advanced diseases;
   • Arm3:Failed with at least one line of standard treatment or intolerance;

5. Patients who have previously undergone neoadjuvant chemotherapy, adjuvant chemotherapy, radiotherapy, or radiochemotherapy for the purpose of curing non metastatic diseases must have a disease-free interval of 6 months from the last chemotherapy and/or radiotherapy to the randomization date.

6. There is at least one measurable lesion that meets the definition of the RECIST 1.1 standard at baseline.

7. ECOG fitness status score: 0 or 1 point.

8. Estimated survival time ≥ 3 months.

Exclusion Criteria:

1. Central nervous system metastasis or meningeal metastasis with clinical symptoms.
2. Have a history of autoimmune diseases, immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation.
3. Active hepatitis B (hepatitis B virus titer>1000 copies/ml or 200 IU/ml); Hepatitis C virus and syphilis infection.
4. Have undergone major organ surgery (excluding puncture biopsy) or have experienced significant trauma within 3 weeks before the first use of the study drug.
5. Known hypersensitivity or intolerance to any component of the study protocol drug or its excipients.