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

Study Overview
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Brief Summary
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Disitamab Vedotin combined therapy locally advanced or metastatic NSCLC Patients with HER2 Alterations.

Detailed Description
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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.

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

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

Intervention / Treatment
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* Drug: RC48+Tislelizumab+carboplatin
* Drug: RC48+Furmonertinib, 1L
* Drug: RC48+Furmonertinib, 2L+


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18 (inclusive) or above, regardless of gender. Histologically or cytologically confirmed locally advanced or metastatic NSCLC, not suitable for radical surgery or radiotherapy (TNM 8th Edition).. 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; 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; 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. There is at least one measurable lesion that meets the definition of the RECIST 1.1 standard at baseline. ECOG fitness status score: 0 or 1 point. Estimated survival time ≥ 3 months. Exclusion Criteria: Central nervous system metastasis or meningeal metastasis with clinical symptoms. Have a history of autoimmune diseases, immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation. Active hepatitis B (hepatitis B virus titer>1000 copies/ml or 200 IU/ml); Hepatitis C virus and syphilis infection. Have undergone major organ surgery (excluding puncture biopsy) or have experienced significant trauma within 3 weeks before the first use of the study drug. Known hypersensitivity or intolerance to any component of the study protocol drug or its excipients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: RC48+PD-1/PD-L1 inhibitor<br> | Drug: RC48+Tislelizumab+carboplatin<br>* RC48+PD-1/PD-L1 inhibitor+chemo in treatment-naive patients harboring HER2 alterations<br>|
| Experimental: Arm 2: RC48+Furmonertinib, 1L<br> | Drug: RC48+Furmonertinib, 1L<br>* RC48+Furmonertinib in treatment-naive patients harboring EGFR mutations as well as HER2 alterations<br>|
| Experimental: Arm 3: RC48+Furmonertinib, 2L+<br> | Drug: RC48+Furmonertinib, 2L+<br>* RC48+Furmonertinib in patients who failed at least one line of standard treatment and harboring HER2 alterations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Percentage of Participants who have a complete response (CR) or partial response (PR) as assessed by investigator according to RECIST 1.1 | Up to 24 months (data cut-off) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate (DCR) Following Treatment in Participants With HER2 alterations Non-Small-Cell Lung Cancer (NSCLC) | Defined as the proportion of participants who have a complete response (CR), partial response (PR) or standard disease (SD) as assessed by investigator according to RECIST 1.1 | Up to 24 months (data cut-off) | 
| Progression-free survival (PFS) Following Treatment in Participants With HER2 alterations Non-Small-Cell Lung Cancer (NSCLC) | Defined as time from randomization until progression per RECIST 1.1 as assessed by investigator, or death due to any cause. | Up to 24 months (data cut-off) | 
| Duration of Response (DoR) Following Treatment in Participants With HER2 alterations Non-Small-Cell Lung Cancer (NSCLC) | Defined as the time from the date of first documented response until date of documented progression as assessed by investigator assessment according to RECIST 1.1. | Up to 24 months (data cut-off) | 
| Overall Survival (OS) Following Treatment in Participants With HER2 alterations Non-Small-Cell Lung Cancer (NSCLC) | Defined as time from randomization until the date of death due to any cause. | Up to 24 months (data cut-off) |