Combination treatment for HER2-positive gastric cancer after first-line therapy

Disitamab Vedotin Combined With Fruquintinib and Tislelizumab in Second-line Treatment for HER2-positive Metastatic Gastric Cancer: A Prospective Phase Ib/II Study

This study is testing a new combination of treatments for people with HER2-positive gastric cancer who didn't respond to their first treatment, to see if it can help them better.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 43 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, radiation, prednisone, Disitamab, Tislezumab, Fruquintinib, immunotherapy
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05982834 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy of a combination therapy involving Disitamab Vedotin, Fruquintinib, and Tislelizumab for patients with HER2-positive gastric cancer who have failed first-line treatment. The study aims to explore the potential of this regimen as a second-line treatment option, leveraging the mechanisms of an anti-HER2 antibody-drug conjugate, an anti-vascular tyrosine kinase inhibitor, and an immunotherapy agent. Eligible participants will be those with measurable lesions and specific HER2 expression levels, ensuring a targeted approach to treatment.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with HER2-positive gastric or gastroesophageal junction adenocarcinoma who have failed first-line therapy.

Not a fit: Patients who have not been diagnosed with HER2-positive gastric cancer or those who have not failed first-line treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with HER2-positive gastric cancer who have exhausted first-line therapies.

How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and targeted therapies in HER2-positive cancers, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. older than18 years of age, gender not limited;
2. the histologic diagnosis of the stomach or gastroesophageal junction adenocarcinoma;
3. immunohistochemical HER2 2 + 3 + or HER2, FISH is positive;
4. at least have a measurable lesions (10 mm or higher spiral CT scan, RECIST 1.1 standard);
5. First-line treatment failure of fluorouracil and the platinum, or to accept containing fluorouracil and platinum adjuvant chemotherapy in patients with recurrence after 6 months;
6. ECOG 0-2, expected survival for 3 months or more;
7. the subjects treated with other damage has been restored, accepting radiotherapy should be ended more than 3 weeks;
8. major organs function is normal, the group within 1 week before the lab test results meet the following criteria: (1) The standard of blood routine examination shall meet:

   1. HB≥80g/L;
   2. ANC ≥1.5×109/L;
   3. PLT ≥75×109/L (2) Biochemical examination shall meet the following standards:

   a. Total bilirubin BIL \< 1.25 \* upper limit of normal (ULN) B. the ALT and AST acuities were 2.5 \* ULN. C. serum creatinine (Cr) of 1.5 or less \* ULN, endogenous creatinine clearance \> 50 ml/min (Cockcroft - Gault formula)
9. participants voluntarily participate in this study, and signed by himself or agent informed consent; Patient compliance is good, can cooperate with the relevant examination, treatment and follow-up.

Exclusion Criteria:

1. history of other malignant tumors within 3 years, have cured except cervical carcinoma in situ or skin basal cell carcinoma;
2. with brain or meningeal metastasis;
3. associated with gastrointestinal obstruction, gastrointestinal bleeding (defecate occult blood + + + and above) or perforation;
4. with active, or have a history and possible recurrence of autoimmune disease of the subjects (such as: Systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or those at high risk (such as those who have received an organ transplant requiring immunosuppressive therapy), However, patients with vitiligo, psoriasis, alopecia, or Grave's disease who did not require systemic treatment within the last 2 years, or patients with hypothyroidism who only needed thyroid hormone replacement therapy, and patients with type I diabetes who only needed insulin replacement therapy could be enrolled;
5. now with interstitial lung disease or pneumonia, pulmonary fibrosis, acute lung diseases, radiation pneumonia;
6. within 4 weeks before delivery for the first time to participate in any other drug clinical research (the use of test drugs shall prevail), unless the participant observation (non intrusive) clinical research;
7. within 4 weeks before the first dose of study treatment used immunosuppressive drugs, Does not include nasal, inhalation or other routes of topical corticosteroids or physiological doses of systemic corticosteroids (i.e., not exceeding 10 mg/ day of prednisone or equivalent doses of other corticosteroids), or short-term (not exceeding 7 days) use of corticosteroids for the prevention or treatment of non-autoimmune allergic diseases;
8. within 4 weeks before the first dose of study treatment or accept the live attenuated plan during the study period. Note: Inactivated virus vaccines for injectable seasonal influenza are permitted for up to 4 weeks prior to initial administration; But live attenuated influenza vaccines are not allowed;
9. within 4 weeks before the first dose of study treatment received major surgery, open chest or craniotomy laparotomy or expected during the research and treatment need to accept of this study major surgery.
10. infected with human immunodeficiency virus (HIV) disease (i.e., an HIV positive), or with other acquired, congenital immunodeficiency disease, or has a history of history of organ transplantation, or stem cell transplantation;
11. chronic active hepatitis b or active active hepatitis c, hepatitis b virus carriers, stable after drug treatment of hepatitis b (DNA drop degree is not higher than 200 iu/mL or copy number Copies \<1000copies/mL) and cured hepatitis C patients (HCV RNA test negative) could be included;
12. with known active tuberculosis;
13. first before 4 weeks with severe infections, or 2 weeks before appear active infection need oral or intravenous antibiotic therapy patients;
14. symptomatic congestive heart failure (New York heart association grade II - IV) or symptomatic or poorly controlled arrhythmia.
15. even give specification treatment still uncontrolled arterial blood pressure (systolic blood pressure or greater acuity 160 MMHG or diastolic blood pressure, 100 MMHG).
16. within 6 months before the selected treatment occurred any arterial thromboembolic events, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack.
17. within 3 months before the group with deep vein thrombosis, pulmonary embolism, or any other serious history of thromboembolism (implantable venous infusion port source sex or catheter thrombosis, or superficial venous thrombosis were not regarded as a "severe" thromboembolism).
18. always have a clear history of neurological or psychiatric disorders, such as memory, epilepsy, dementia, compliance, or the peripheral nervous system disorder;
19. alcohol dependence or nearly 1 year has a history of drug or drug abuse;
20. pregnancy or lactation women; Those who are fertile but do not take adequate contraceptive measures;
21. may lead to the following results of other acute or chronic diseases, mental illness or abnormal laboratory values: participated in or study drug dosage associated with an increased risk, or interfere with the interpretation of results, and according to the researcher's judgment will be patient as does not conform to participate in this study.

Where this trial is running

Shanghai, Shanghai

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Xiaodong Zhu, M.D.,Ph.D.

Conditions HER2-positive Gastric Cancer; Immunotherapy