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

NCT06123494 | Recruiting Phase 3

• 1 other identifier: SHR-A1811-308
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HER2-positive Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  defined as the time from date of randomization until death from any cause.

  Time from date of randomization until death (due to any cause), up to approximately 42 months

Secondary Outcomes (7)

• Progression-free survival (PFS)

  Time from date of randomization until first objective radiographic disease progression or death (due to any cause) whichever occurs first, up to approximately 42 months

• Objective response rate (ORR)

  From start of treatment to date of documented disease progression, up to approximately 42 months

• Duration of response (DoR)

  Time from initial response (CR or PR) to date of documented disease progression or death (due to any cause) whichever occurs first, up to approximately 42 months

• Disease control rate (DCR)

  From start of treatment to date of documented disease progression, up to approximately 42 months

• AE and SAE

  From time subjects signs informed consent form up to 40 days after last study dose

Study Arms (2)

SHR-A1811

EXPERIMENTAL

Drug: SHR-A1811

The investigators' choice

ACTIVE COMPARATOR

Drug: Ramucirumab / Paclitaxel/ Docetaxel/ Irinotecan

Interventions

SHR-A1811 DRUG

SHR-A1811 6.4 mg/kg IV infusion every 3 weeks on Day 1 of each 21-day cycle

SHR-A1811

Ramucirumab / Paclitaxel/ Docetaxel/ Irinotecan DRUG

Ramucirumab 8mg/kg，D 1,15 + Paclitaxel 80mg/m2，D1,8,15，Q4W; Paclitaxel 80mg/m2，D1,8,15，Q4W; Docetaxel 75mg/m2，D1，Q3W; Irinotecan 150mg/m2，D1，Q2W.

The investigators' choice

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

MeSH Terms

Interventions

Ramucirumab; Paclitaxel; Docetaxel; Irinotecan

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Camptothecin; Alkaloids; Heterocyclic Compounds

Central Study Contacts

Yang Wu

CONTACT

0518-82342973; yang.wu.yw96@hengrui.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2023
• First Posted: November 8, 2023
• Study Start: January 9, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: January 16, 2024

Record last verified: 2024-01

Locations

CN (1)