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

Sun Yat-sen University

Status and phase: Not yet enrolling; Phase 2

Conditions: ERBB2 Mutation-Related Tumors; RC48; Disitamab Vedotin; Non Small Cell Lung Cancer

Treatments: Drug: RC48+Furmonertinib, 1L; Drug: RC48+Tislelizumab+carboplatin; Drug: RC48+Furmonertinib, 2L+

Study type: Interventional

Funder types: Other

Identifiers

NCT05847764

RCVDODIIR006

Details and patient eligibility

About

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

Full description

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.

Enrollment: 95 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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95 participants in 3 patient groups

Arm 1: RC48+PD-1/PD-L1 inhibitor

Experimental group

Treatment:

Drug: RC48+Tislelizumab+carboplatin

Arm 2: RC48+Furmonertinib, 1L

Experimental group

Treatment:

Drug: RC48+Furmonertinib, 1L

Arm 3: RC48+Furmonertinib, 2L+

Experimental group

Treatment:

Drug: RC48+Furmonertinib, 2L+