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.

Study Overview

• Status: Not yet recruiting
• Conditions: Non Small Cell Lung Cancer; ERBB2 Mutation-Related Tumors; RC48; Disitamab Vedotin
• Intervention / Treatment: Drug: RC48+Tislelizumab+carboplatin; Drug: RC48+Furmonertinib, 1L; Drug: RC48+Furmonertinib, 2L+

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.

• Study Type: Interventional
• Enrollment (Anticipated): 95
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Li PI Zhang, MD; Phone Number: 020-87343421; Email: zhangli@sysucc.org.cn

Study Locations

• China
  • Guanzhou, China
    • SunYat-senU
    • Contact: Li Zhang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Li PI Zhang, MD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): May 1, 2025

Study Registration Dates

• First Submitted: March 21, 2023
• First Submitted That Met QC Criteria: May 5, 2023
• First Posted (Actual): May 8, 2023

Study Record Updates

• Last Update Posted (Actual): May 8, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Carboplatin
• Other Study ID Numbers: RCVDODIIR006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No