SHR-A1811 for Subjects With Her2-positive Gastric Cancer and Gastroesophageal Junction Adenocarcinoma After Progression on or After First-line Anti-HER2 Therapy-containing Regimen

Hengrui Medicine

Status and phase

Enrolling

Phase 3

Conditions

HER2-positive Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma

Treatments

Drug: SHR-A1811

Drug: Ramucirumab / Paclitaxel/ Docetaxel/ Irinotecan

Study type

Interventional

Funder types

Industry

Identifiers

NCT06123494

SHR-A1811-308

Details and patient eligibility

About

This study will assess the efficacy and safety of SHR-A1811 compared with treatment chosen by the investigator in participants with HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+) gastric or GEJ adenocarcinoma (based on [American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines who have progressed on or after a first-line anti-HER2 therapy-containing regimen.

Enrollment

360 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age 18-75 years old, male and female;
Histologically or cytologically confirmed gastric or gastroesophageal junction adenocarcinoma, and unresectable locally advanced or metastatic disease
Prior anti-HER-2 containing treatment
Progression on or after first-line standard treatment (Prior neoadjuvant or adjuvant therapy can be counted as a line of therapy if the subject progressed on or within 6 months of completing neoadjuvant or adjuvant therapy);
Centrally confirmed HER2-positive (IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH) as classified by ASCO-CAP on a tumor biopsy
At least one measurable lesion according to the solid tumor response Evaluation Criteria (RECIST 1.1);
ECOG: 0-1;
Expected survival ≥12 weeks;
Good blood reserve and liver, kidney and coagulation function;
Willing to provide informed consent for study participation.

Exclusion criteria

Receive the last dose of anti-cancer therapy(including chemotherapy, radiotherapy, biological therapy, targeted therapy or immunotherapy) within 4 weeks, prior to the first dose;
Known allergies to monoclonal antibodies and inactive ingredients of this product, and allergies to paclitaxel, docetaxel, and irinotecan concurrently;
The toxicity of prior anti-tumor therapy did not recover to the level specified by CTCAE v5.0 grade evaluation ≤ Grade 1 or inclusion/exclusion criteria;
Clinically active central nervous system metastases;
Uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
Clinically significant gastrointestinal disorder by the opinion of Investigator;
Has a history of immunodeficiency, including a positive HIV test;
During the screening visits and before the first dose, unexplained fever > 38.5℃, severe infection (CTC-AE > Grade 2), and active pulmonary inflammation were indicated by screening imaging;
Subjects with interstitial pneumonia or with ≥ grade 3 interstitial pneumonia during prior treatment with immune checkpoint inhibitors;
Active hepatitis B(HBV DNA ≥ 500 IU/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA above the lower limit of detection of the analytical method);
Clinically significant cardiovascular disease ,such as severe/unstable angina, symptomatic congestive heart failure (NYHA ≥ Class II.), clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention, myocardial infarction within 6 months before the first dose, cerebrovascular accident (including transient ischemic attack); QTcF of 12-lead ECG was ≥470 ms; Left ventricular ejection fraction <50%; Clinically uncontrolled hypertension;
Had other malignancies with 5 years;
Pregnant or lactating women;
Other factors that might have led to drop out the study by the investigator opinion.