A Study of SHR-A1811 in Subjects With Advanced Malignant Solid Tumors

A Phase 1 Multi-Country, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of SHR-A1811 in HER2 Expressing or Mutated Advanced Malignant Solid Tumor Subjects

This is an open-label, two-part study to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of SHR-A1811 and preliminary anti-tumor efficacy in HER2 expressing or mutated advanced malignant solid tumor subjects.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: SHR-A1811

• Study Type: Interventional
• Enrollment (Actual): 396
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia, 3004
    • Alfred Hospital
  • New South Wales
    • Macquarie, New South Wales, Australia, 2109
      • Macquarie University Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Southern Oncology Clinical Research Unit
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Peninsula and South Eastern Haematology & Oncology Group
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network
• China
  • Anhui
    • Bengbu, Anhui, China, 233000
      • The First Affiliated Hospital Of Bengbu Medical College
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences
  • Fuzhou
    • Fujian, Fuzhou, China, 350000
      • Fujian Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510120
      • Nanfang Hospital
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430062
      • Zhongnan Hospital of Wuhan University
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University
    • Changsha, Hunan, China, 410031
      • Hunan Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital
    • Nanjing, Jiangsu, China, 210000
      • Jiangsu Province Hospital
  • Liaoning
    • Shengyang, Liaoning, China, 110022
      • Shengjing Hospital of China Medical University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan Unversity Zhongshan Hospital
    • Shanghai, Shanghai Municipality, China, 200032
      • Shanghai Jiao Tong University School of Medicine Renji Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • Shanxi Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610042
      • Sichuan Cancer Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300181
      • Tianjin medical university cancer institute&hoospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310014
      • Zhejiang Provincial People's Hospital
    • Hangzhou, Zhejiang, China, 310014
      • The Second Affiliated Hospital Zhejiang University School of Medicine
• South Korea
  • Seoul, South Korea, 3080
    • Seoul National University Hospital
  • Seoul, South Korea, 5505
    • Asan Medical Center
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Tainan City, Taiwan, 70457
    • National Cheng Kung University Hospital
  • Taoyuan District, Taiwan, 333
    • Chang Gung Memorial Hospital, Linkou
• United States
  • New York
    • The Bronx, New York, United States, 10461
      • Montefiore-Einstein Center for Cancer Care
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Advanced/unresectable or metastatic solid tumor with HER2 expression or mutation that is refractory to or intolerable with standard treatment, or for which no standard treatment is available
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• LVEF ≥ 50% by either ECHO or MUGA
• Has adequate renal and hepatic function
• Female subjects agree not to be pregnant or lactating from beginning of the study screening until 6 months after receiving the last treatment

Exclusion Criteria:

• History of clinically significant lung diseases (e.g., interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or suspected to have these diseases by imaging at screening period
• Known hereditary or acquired bleeding and thrombotic tendency

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Dose escalation	Drug: SHR-A1811; be administered via intravenous (IV) infusion
Experimental: Part 2 PK expansion	Drug: SHR-A1811; be administered via intravenous (IV) infusion
Experimental: Part 3 Indication expansion	Drug: SHR-A1811; be administered via intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events (AEs)	Frequency and seriousness of treatment emergent adverse events (TEAEs)	From Day1 to 90 days after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameter: Tmax of SHR-A1811	Time to maximal concentration (Tmax) of SHR-A1811	Through study completion, an average of 1 year
PK parameter: Cmax of SHR-A1811	Maximal concentration (Cmax) of SHR-A1811	Through study completion, an average of 1 year
PK parameter: AUC0-t of SHR-A1811	AUC computed from time zero to the time of the last quantifiable concentration (AUC0-t) of SHR-A1811	Through study completion, an average of 1 year
Immunogenicity of SHR-A1811	Including anti-drug antibody and/or neutralizing antibody	Through study completion, an average of 1 year
Tumor response using RECIST 1.1	RECIST=Response Evaluation Criteria in Solid Tumors Assessment of tumor response until disease progression or death to evaluate the efficacy of SHR-A1811 up to 30 months	From first dose to disease progression or death, whichever comes first, up to 30 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Collaborators: Atridia Pty Ltd.

Publications and helpful links

General Publications

• Yao H, Yan M, Tong Z, Wu X, Ryu MH, Park JJ, Kim JH, Zhong Y, Zhao Y, Voskoboynik M, Yin Y, Liu K, Kaubisch A, Liu C, Zhang J, Wang S, Im SA, Ganju V, Barve M, Li H, Ye C, Roy AC, Bai LY, Yen CJ, Gu S, Lin YC, Wu L, Bao L, Zhao K, Shen Y, Rong S, Zhu X, Song E. Safety, Efficacy, and Pharmacokinetics of SHR-A1811, a Human Epidermal Growth Factor Receptor 2-Directed Antibody-Drug Conjugate, in Human Epidermal Growth Factor Receptor 2-Expressing or Mutated Advanced Solid Tumors: A Global Phase I Trial. J Clin Oncol. 2024 Oct 10;42(29):3453-3465. doi: 10.1200/JCO.23.02044. Epub 2024 Jun 20.

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2020
• Primary Completion (Actual): June 4, 2025
• Study Completion (Actual): June 4, 2025

Study Registration Dates

• First Submitted: June 18, 2020
• First Submitted That Met QC Criteria: June 22, 2020
• First Posted (Actual): June 24, 2020

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SHR-A1811-I-101

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