Treatment for HER2-positive gastric cancer after first-line therapy

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

This study is testing a new treatment called SHR-A1811 to see if it can help people with HER2-positive gastric cancer who haven't improved after their first treatment.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 360 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Jiangsu HengRui Medicine Co., Ltd. (industry)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06123494 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of SHR-A1811 in patients with HER2-positive gastric cancer or gastroesophageal junction adenocarcinoma who have progressed after receiving first-line anti-HER2 therapy. Participants will receive SHR-A1811 and be compared to a treatment chosen by their healthcare provider. The study aims to determine if SHR-A1811 can provide better outcomes than existing treatment options for these patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with confirmed HER2-positive gastric or gastroesophageal junction adenocarcinoma who have progressed after first-line anti-HER2 therapy.

Not a fit: Patients who have not received prior anti-HER2 therapy or those with resectable disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with advanced HER2-positive gastric cancer who have limited choices after first-line therapy.

How similar studies have performed: Other studies have shown promising results with similar approaches targeting HER2-positive cancers, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

1. Age 18-75 years old, male and female;
2. Histologically or cytologically confirmed gastric or gastroesophageal junction adenocarcinoma, and unresectable locally advanced or metastatic disease
3. Prior anti-HER-2 containing treatment
4. 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);
5. 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
6. At least one measurable lesion according to the solid tumor response Evaluation Criteria (RECIST 1.1);
7. ECOG: 0-1;
8. Expected survival ≥12 weeks;
9. Good blood reserve and liver, kidney and coagulation function;
10. Willing to provide informed consent for study participation.

Exclusion Criteria:

1. 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;
2. Known allergies to monoclonal antibodies and inactive ingredients of this product, and allergies to paclitaxel, docetaxel, and irinotecan concurrently;
3. 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;
4. Clinically active central nervous system metastases;
5. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
6. Clinically significant gastrointestinal disorder by the opinion of Investigator;
7. Has a history of immunodeficiency, including a positive HIV test;
8. 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;
9. Subjects with interstitial pneumonia or with ≥ grade 3 interstitial pneumonia during prior treatment with immune checkpoint inhibitors;
10. 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);
11. 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;
12. Had other malignancies with 5 years;
13. Pregnant or lactating women;
14. Other factors that might have led to drop out the study by the investigator opinion.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai East Hospital — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Yang Wu

Conditions: HER2-positive Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma