Disitamab Vedotin, ERBB2 Mutation-Related Tumors, Non Small Cell Lung Cancer, RC48
Conditions
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.
Interventions
DRUGRC48+Tislelizumab+carboplatin
RC48+PD-1/PD-L1 inhibitor+chemo in treatment-naive patients harboring HER2 alterations
DRUGRC48+Furmonertinib, 1L
RC48+Furmonertinib in treatment-naive patients harboring EGFR mutations as well as HER2 alterations
DRUGRC48+Furmonertinib, 2L+
RC48+Furmonertinib in patients who failed at least one line of standard treatment and harboring HER2 alterations
Sponsors
Sun Yat-sen University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to 24 months (data cut-off) | Percentage of Participants who have a complete response (CR) or partial response (PR) as assessed by investigator according to RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) Following Treatment in Participants With HER2 alterations Non-Small-Cell Lung Cancer (NSCLC) | Up to 24 months (data cut-off) | 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 |
| Progression-free survival (PFS) Following Treatment in Participants With HER2 alterations Non-Small-Cell Lung Cancer (NSCLC) | Up to 24 months (data cut-off) | Defined as time from randomization until progression per RECIST 1.1 as assessed by investigator, or death due to any cause. |
| Duration of Response (DoR) Following Treatment in Participants With HER2 alterations Non-Small-Cell Lung Cancer (NSCLC) | Up to 24 months (data cut-off) | 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. |
| Overall Survival (OS) Following Treatment in Participants With HER2 alterations Non-Small-Cell Lung Cancer (NSCLC) | Up to 24 months (data cut-off) | Defined as time from randomization until the date of death due to any cause. |
Countries
China
Contacts
Primary ContactLi PI Zhang, MD
Outcome results
None listed