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

Official title

A Phase 3, Multicenter, Randomized, Open-label Study of SHR-A1811 (HER2-ADC) Compared With the Chemotherapy Treatment Chosen by the Investigators for Subjects With HER2-positive Metastatic and/or Unresectable Gastric Cancer or Gastroesophageal Junction Adenocarcinoma Who Have Progressed on or After First-line Anti-HER2 Therapy-containing Regimen

Overview

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.

Interventions

• Drug SHR-A1811
  SHR-A1811 6.4 mg/kg IV infusion every 3 weeks on Day 1 of each 21-day cycle
• Drug Ramucirumab / Paclitaxel/ Docetaxel/ Irinotecan
  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.

Primary outcome measures

• Overall survival (OS) [Time frame: Time from date of randomization until death (due to any cause), up to approximately 42 months]

Secondary outcome measures (7)

• Progression-free survival (PFS) [Time frame: 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) [Time frame: From start of treatment to date of documented disease progression, up to approximately 42 months]
• Duration of response (DoR) [Time frame: 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) [Time frame: From start of treatment to date of documented disease progression, up to approximately 42 months]
• AE and SAE [Time frame: From time subjects signs informed consent form up to 40 days after last study dose]
• Immunogenicity indicators of SHR-A1811: including anti-SHR-A1811 antibodies (ADA and neutralizing antibodies) [Time frame: approximately 42 months]
• Serum concentrations of SHR-A1811 toxin-binding antibodies and free toxin SHR169265 [Time frame: approximately 42 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai East Hospital — Shanghai

Identifiers

NCT: NCT06123494 · SHR-A1811-308

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗