RC48 Combined With EGFR or HER2 TKI for Locally Advanced or Metastatic NSCLC Patients With HER2 Alterations

Disitamab Vedotin（RC48）Combined With EGFR or HER2 TKI for Locally Advanced or Metastatic NSCLC Patients With HER2 Alterations

Disitamab Vedotin（RC48）combined with EGFR or HER2 TKIs in 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; Disitamab Vedotin; ERBB2 Gene Duplication
• Intervention / Treatment: Drug: Disitamab Vedotin; Drug: third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib); Drug: pyrotinib

Detailed Description

This study will explore the treatment of locally advanced or metastatic non-small cell lung cancer with HER2 mutation, amplification, or HER2 protein overexpression, using Disitamab Vedotin（RC48）combined with EGFR or HER2 TKIs, in the aim of providing new treatment strategies for lung cancer patients with HER2 pathway activation.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jie Wang, Dr; Phone Number: 010-87788219; Email: zlhuxi@163.com

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. HER2 alterations include HER2 gene mutations, gene amplification and HER2 protein over-expression;

4. Number of treatment lines:

   • Arm1: patients who have not previously received systemic treatment for advanced diseases;
   • Arm2: Previously received first line of third-generation EGFR-TKIs treatment with local progression, oligometastasis, or slow progression, and evaluated by the researchers to continue to benefit from third-generation EGFR-TKIs treatment;
   • Arm3: Previously received first line of third-generation EGFR-TKIs treatment with extensively progression, and evaluated by the researchers not likely to continue to benefit from third-generation EGFR-TKIs treatment;
5. There is at least one measurable lesion that meets the definition of the RECIST 1.1 standard at baseline.
6. ECOG fitness status score: 0 or 1 point.

Exclusion Criteria:

1. Central nervous system metastasis or meningeal metastasis with clinical symptoms.
2. Known hypersensitivity or intolerance to any component of the study protocol drug or its excipients.
3. Have a history of severe cardiovascular disease.
4. Have a history of interstitial lung disease or drug-induced interstitial lung disease requiring steroids treatment; radiation pneumonia.
5. Have a history of neurological disorders or mental illnesses, including epilepsy or dementia.
6. Pregnant or lactating women.
7. The researcher believes that the subject is not suitable to participate in this clinical study due to other reasons.

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: Arm1: Treatment Naive NSCLC; RC48+third-generation EGFR TKIs in treatment-naive patients harboring EGFR mutation and HER2 alterations	Drug: Disitamab Vedotin; RC48+third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib) in treatment naive NSCLC; Other Names: RC48; Drug: third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib); RC48+third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib) after EGFR-TKIs progression
Experimental: Arm2: Locally Progressed; This cohort includes ERBB2 altered patients after third-generation EGFR-TKIs treatment with locally or slowly progressed disease, who may continue to benefit from third-generation EGFR-TKIs treatment under investigators' evaluation.	Drug: Disitamab Vedotin; RC48+third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib) in treatment naive NSCLC; Other Names: RC48; Drug: third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib); RC48+third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib) after EGFR-TKIs progression
Experimental: Arm3: Extensively Progressed; This cohort includes ERBB2 altered patients after third-generation EGFR-TKIs treatment with extensively progressed disease, who may be less likely to benefit from third-generation EGFR-TKIs treatment under investigators' evaluation.	Drug: Disitamab Vedotin; RC48+third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib) in treatment naive NSCLC; Other Names: RC48; Drug: pyrotinib; RC48+pyrotinib after EGFR-TKIs progression

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: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 28, 2023
• First Submitted That Met QC Criteria: December 28, 2023
• First Posted (Actual): December 29, 2023

Study Record Updates

• Last Update Posted (Actual): December 29, 2023
• Last Update Submitted That Met QC Criteria: December 28, 2023
• Last Verified: December 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Protein Kinase Inhibitors; Immunoconjugates; Osimertinib; Aflutinib; Disitamab vedotin
• Other Study ID Numbers: RCVDODIIR010

Drug and device information, study documents

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