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

Phase 2

Not yet recruiting

• Conditions: Disitamab Vedotin; ERBB2 Mutation-Related Tumors; Non Small Cell Lung Cancer; ERBB2 Gene Duplication
• Interventions: Drug: Disitamab Vedotin; Drug: third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib); Drug: pyrotinib

• Registration Number: NCT06185400
• Lead Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Brief Summary

Disitamab Vedotin（RC48）combined with EGFR or HER2 TKIs in 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 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 Timeline

• Study First Submitted: 2023-11-28
• Status Verified: 2023-12
• Study First Submitted QC: 2023-12-28
• Last Update Submitted: 2023-12-28
• Study First Posted: 2023-12-29
• Last Update Posted: 2023-12-29
• Study Start: 2024-02-01
• Primary Completion: 2025-07-01
• Study Completion: 2026-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 108

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm2: Locally Progressed	third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib)	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.
Arm1: Treatment Naive NSCLC	third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib)	RC48+third-generation EGFR TKIs in treatment-naive patients harboring EGFR mutation and HER2 alterations
Arm1: Treatment Naive NSCLC	Disitamab Vedotin	RC48+third-generation EGFR TKIs in treatment-naive patients harboring EGFR mutation and HER2 alterations
Arm2: Locally Progressed	Disitamab Vedotin	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.
Arm3: Extensively Progressed	Disitamab Vedotin	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.
Arm3: Extensively Progressed	pyrotinib	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.