A Study of SHR-A1811 in First-line Treatment of Patients With Advanced or Metastatic Non-small Cell Lung Cancer With HER2 Mutations

A Randomized, Open-Label, Multicenter Phase III Study of SHR-A1811 for First-Line Treatment in Subjects With HER2-Mutated Advanced or Metastatic Non-Small Cell Lung Cancer

The study is being conducted to evaluate the efficacy, and safety of SHR-A1811 versus Standard of Care as first-line treatment of advanced or metastatic Non-Small Cell Lung Cancer with HER2- Mutations

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer With HER2- Mutations
• Intervention / Treatment: Drug: SHR-A1811; Drug: PD-1/PD-L1 inhibitors、Pemetrexed/ Paclitaxel、Carboplatin/ Cisplatin

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: You Li; Phone Number: 0518-81220121; Email: you.li.yl1@hengrui.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200030
      • Recruiting
      • Shanghai Chest Hospital
      • Principal Investigator: Shun Lu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Able and willing to provide a written informed consent
2. 18-75 years old (inclusive of both ends)
3. ECOG score of 0 or 1.
4. Patients with histologically or cytologically confirmed advanced or metastatic NSCLC.
5. Subjects with central laboratory- confirmed functional HER2 mutations
6. No prior systemic antitumor therapy (including investigational agents) for advanced or metastatic NSCLC.
7. Have at least one measurable lesion outside the central nervous system that meets the criteria defined by RECIST v1.1
8. Protocol-defined adequate organ function including cardiac, renal, hepatic function

Exclusion Criteria:

1. Mixed lung cancer with small cell components and sarcomatoid carcinoma confirmed by histology or cytology.
2. Concurrently carrying other driver gene mutations, and targeted drugs for such driver gene mutations have been approved for market release.
3. Subjects with untreated or active metastasis of central nervous system (CNS) tumors, or a history of meningeal metastasis or current meningeal metastasis.
4. With poorly controlled tumor-related pain.
5. previous or current with other malignancies.
6. Subjects with a history of interstitial pneumonia/non-infectious pneumonia requiring hormone therapy, or current interstitial pneumonia/non-infectious pneumonia.
7. Subjects with active or previous autoimmune diseases.
8. Subjects with uncontrolled or severe cardiovascular diseases.
9. Subjects with active hepatitis B or hepatitis C.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-A1811	Drug: SHR-A1811; Drug: SHR-A1811 administered intravenously every 3 weeks (Q3W)
Active Comparator: Standard of Care（PD-1/ PD-L1 inhibitors、Pemetrexed/ Paclitaxel、Carboplatin/ Cisplatin）	Drug: PD-1/PD-L1 inhibitors、Pemetrexed/ Paclitaxel、Carboplatin/ Cisplatin; Drug: PD-1/PD-L1 inhibitors administered intravenously every 3 weeks (Q3W) Drug: Pemetrexed Based on the investigator's choice was administered intravenously every 3 weeks (Q3W) Drug: Paclitaxel Based on the investigator's choice was administered intravenously every 3 weeks (Q3W) Drug: Carboplatin Based on the investigator's choice was administered intravenously every 3 weeks (Q3W) Drug: Cisplatin Based on the investigator's choice was administered intravenously every 3 weeks (Q3W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) based on blinded independent central review (BICR)	Defined as time from randomization until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR)	Until progression, assessed up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Defined as time from randomization until the date of death due to any cause	Until death, assessed up to approximately 3 years
Progression Free Survival (PFS) by investigator assessment	Defined as time from randomization until progression per RECIST 1.1 as assessed by the investigator	Until progression, assessed up to approximately 2 years
Incidence and severity of adverse events (AEs)/serious adverse events (SAEs)	Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0	until to 90 days after the last dose，assessed up to approximately 3 years

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: May 21, 2024
• First Submitted That Met QC Criteria: May 24, 2024
• First Posted (Actual): May 28, 2024

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 18, 2026
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Cisplatin; CP protocol
• Other Study ID Numbers: SHR-A1811-310

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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