Combination therapy of Disitamab Vedotin and Trastuzumab for HER2 positive gastric cancer

Phase I/II Clinical Study of the Combination of Disitamab Vedotin and Trastuzumab in the Treatment of HER2 Positive Gastric/Gastroesophageal Junction Tumors With Previous Systemic Therapy Failure

This study is testing a new combination of two drugs, Disitamab Vedotin and Trastuzumab, to see if it can help people with advanced HER2 positive gastric cancer who haven't responded to other treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Zhejiang Cancer Hospital (Academic / other)
• Drugs / interventions: immunotherapy, Disitamab, trastuzumab, chemotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06572319 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of a combination therapy using Disitamab Vedotin and Trastuzumab in patients with advanced HER2 positive gastric cancer and gastroesophageal junction adenocarcinoma. It is a single center, open-label study that aims to improve drug penetration into tumors by utilizing a combination of antibody-drug conjugates and naked antibodies. The trial is designed to explore new treatment options for patients who have not responded to first-line systemic therapies. Participants will be monitored for treatment outcomes and potential side effects throughout the study.

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 experienced treatment failure with at least one prior systemic therapy.

Not a fit: Patients with HER2 negative tumors or those who have not received prior systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective therapy option for patients with advanced HER2 positive gastric cancer.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in HER2 positive cancers, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1\. Sign the informed consent form; 2.18-75 years old (including 18 years old, excluding 75 years old), gender not limited; 3. The pathological histology confirmed by pathology is adenocarcinoma of the gastric/gastroesophageal junction; 4. HER2 positive tumor criteria (primary tumor or metastatic lesion, HER2 positive is defined as IHC 2+/FISH+(HER2: CEP17 ratio ≥ 2.0) or IHC (3+). Using the criteria for interpreting HER2 in gastric cancer 5. Recurrent or metastatic diseases that cannot be surgically treated, with at least one measurable lesion (RECIST 1.1 criteria) in the subject and an estimated survival time of at least 12 weeks; 6. ECOG score ranges from 0 to 1 points; 7. At least first-line systemic therapy has failed (regardless of whether it includes anti-HER2 monoclonal antibody therapy); 8. Having sufficient bone marrow, liver and kidney function:

* Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets ≥ 90 × 109/L, or
* hemoglobin ≥ 9g/dL;
* ALT or AST levels without liver metastasis are less than 2.5 times the upper limit of the normal range; When liver metastasis occurs, ALT or AST is less than 5 times the upper limit of the normal range; Serum bilirubin is 1.5 times lower than the upper limit of the normal reference range;
* Serum creatinine is lower than 1.5 times the upper limit of the normal reference range or creatinine clearance rate is ≥ 40ml/min; 9. Women of childbearing age and their spouses are willing to use effective contraceptive methods within the last 7 months of treatment.

Exclusion Criteria:

1. Known to be allergic to the received therapeutic drugs or excipients;
2. Baseline LVEF\<50% (measured by echocardiography or MUGA);
3. Previously received treatment with anti-HER2 ADC drugs;
4. Individuals who have undergone systemic immunotherapy, biologic therapy, or participated in any clinical drug trials within the past 2 weeks;
5. Those who have undergone surgery within 3 weeks before the start of the experimental treatment and have not fully recovered;
6. Patients with uncontrolled central nervous system (CNS) metastases or epilepsy requiring medication treatment;
7. Serious systemic diseases. Such as infected or uncontrolled diabetes;
8. Suffering from other malignant tumors within 5 years, except for non melanoma skin cancer and cervical carcinoma in situ;
9. Clinically symptomatic active coronary heart disease, cardiomyopathy, or congestive heart failure, NYHA III-IV; uncontrolled hypertension (systolic blood pressure\>180 mmHg or diastolic blood pressure\>100 mmHg), clinically symptomatic heart valve disease, or high-risk arrhythmia;
10. Patients receiving long-term or high-dose corticosteroid treatment (inhaled steroids or short-term oral steroids are allowed to resist vomiting or promote appetite)
11. Individuals without legal capacity, those whose medical or ethical reasons affect the continuation of research;
12. Pregnant and lactating female patients, or those who wish to become pregnant during treatment;
13. Uncontrolled pleural and peritoneal effusion;
14. There is a persistent infection of\>level 2 (CTC-AE 4.0); Wounds, ulcers, or fractures that cannot heal, or patients with a history of organ transplantation;
15. There are unresolved toxicity levels\>1 caused by any previous treatment/procedure (CTC-AE 4.0, excluding hair loss, anemia, and hypothyroidism);
16. After comprehensive assessment of the patient's condition by the researchers, it is deemed that they are not suitable to participate in this study;
17. Simultaneously participating in another clinical study.

Where this trial is running

Hangzhou, Zhejiang

• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Jieer Ying, M.D. — Zhejiang Cancer Hospital
• Study coordinator: Jieer Ying, M.D.

Conditions HER2-positive Gastric Cancer; HER2-positive Gastroesophageal Junction Adenocarcinoma; HER-2; ADC; Disitamab Vedotin; trastuzumab