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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (7)

• Progression-free survival (PFS) [Срок оценки: 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) [Срок оценки: From start of treatment to date of documented disease progression, up to approximately 42 months]
• Duration of response (DoR) [Срок оценки: 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) [Срок оценки: From start of treatment to date of documented disease progression, up to approximately 42 months]
• AE and SAE [Срок оценки: 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) [Срок оценки: approximately 42 months]
• Serum concentrations of SHR-A1811 toxin-binding antibodies and free toxin SHR169265 [Срок оценки: approximately 42 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai East Hospital — Шанхай

Идентификаторы

NCT: NCT06123494 · SHR-A1811-308

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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