Clinical trial NCT05847764: Disitamab Vedotin Combined Therapy for Locally Advanced or Metastatic NSCLC Patients With HER2 Alterations
Official title: Disitamab Vedotin Combined Therapy for Locally Advanced or Metastatic NSCLC With HER2 Alterations, a Phase II Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
ERBB2 Mutation-Related Tumors
RC48
Disitamab Vedotin
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2023-05-08
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment in Participants With HER2 alterations Non-Small-Cell Lung Cancer (NSCLC)
timeFrame: Up to 24 months (data cut-off)
Secondary outcomes:
measure: Disease control rate (DCR) Following Treatment in Participants With HER2 alterations Non-Small-Cell Lung Cancer (NSCLC)
timeFrame: Up to 24 months (data cut-off)
measure: Progression-free survival (PFS) Following Treatment in Participants With HER2 alterations Non-Small-Cell Lung Cancer (NSCLC)
timeFrame: Up to 24 months (data cut-off)
measure: Duration of Response (DoR) Following Treatment in Participants With HER2 alterations Non-Small-Cell Lung Cancer (NSCLC)
timeFrame: Up to 24 months (data cut-off)
measure: Overall Survival (OS) Following Treatment in Participants With HER2 alterations Non-Small-Cell Lung Cancer (NSCLC)
timeFrame: Up to 24 months (data cut-off)
Other outcomes:
Locations:
city: Guanzhou
country: China
facility: SunYat-senU
Study officials:
affiliation: Sun Yat-sen University
name: Li PI Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: