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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Not yet enrolling; Phase 2

Conditions: ERBB2 Mutation-Related Tumors; ERBB2 Gene Duplication; Disitamab Vedotin; Non Small Cell Lung Cancer

Treatments: Drug: Disitamab Vedotin; Drug: third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib); Drug: pyrotinib

Study type: Interventional

Funder types: Other

Identifiers

NCT06185400

RCVDODIIR010

Details and patient eligibility

About

Disitamab Vedotin（RC48）combined with EGFR or HER2 TKIs in locally advanced or metastatic NSCLC Patients with HER2 Alterations.

Full 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.

Enrollment: 108 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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108 participants in 3 patient groups

Arm1: Treatment Naive NSCLC

Experimental group

Description:

RC48+third-generation EGFR TKIs in treatment-naive patients harboring EGFR mutation and HER2 alterations

Treatment:

Drug: third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib)

Drug: Disitamab Vedotin

Arm2: Locally Progressed

Experimental group

Description:

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.

Treatment:

Drug: third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib)

Drug: Disitamab Vedotin

Arm3: Extensively Progressed

Experimental group

Description:

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.

Treatment:

Drug: pyrotinib

Drug: Disitamab Vedotin