RC48 Plus AK104 as First-line Treatment for HER2-overexpressing Advanced Gastric Cancer

Trial Title: RC48 Plus AK104 as First-line Treatment for HER2-overexpressing Advanced Gastric Cancer

NCT ID: NCT06492317

Condition: HER2-positive Gastric Cancer

Conditions: Official terms:
Stomach Neoplasms
Disitamab vedotin

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Disitamab Vedotin
Description: Disitamab Vedotin: 2.5mg/kg, d1, ivdrip, Q2W (every 2 weeks)
Arm group label: Disitamab vedotin plus cadonilimab

Other name: RC48

Intervention type: Drug
Intervention name: Cadonilimab
Description: Cadonilimab: 6mg/kg, d1, ivdrip, Q2W (every 2 weeks)
Arm group label: Disitamab vedotin plus cadonilimab

Other name: AK104

Summary: A single-arm, single-center phase II trial study to assess the efficacy and safety of disitamab vedotin plus cadonilimab as first-line therapy for HER2-overexpressing advanced stomach carcinoma

Detailed description: This study is a prospective, single-arm, single-center phase II trial. The purpose of the trial is evaluated Disitamab Vedotin (RC48) plus Cadonilimab (AK104) as first-line therapy for HER2-overexpressing advanced stomach carcinoma, and also check the adverse events (AEs) when participants are administered the combination treatment regimen. This study will include patients with HER2-overexpressing, locally advanced unresectable or metastatic gastric/gastroesophageal junction cancer who have not previously received systemic treatment including chemotherapy, targeted therapy, and immunotherapy. Enrolled patients will be treated with disitamab vedotin (2.5mg/kg, D1, ivdrip, Q2W) combined with cadonilimab (6mg/kg, D1, ivdrip, Q2W) until progressive disease (PD) or intolerable toxicity.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Age: more than 18 years, gender is not limited; 2. Confirmed locally advanced or distant metastasis gastric or gastroesophageal junction adenocarcinoma that is inoperable by pathological examination; 3. Confirmed HER2 2+or 3+ by immunohistochemistry (IHC); 4. At least 1 measurable lesion as determined by RECIST 1.1; 5. There is no prior systematic treatment, or the patient has received neoadjuvant/adjuvant chemotherapy, and the disease progresses or relapses more than 6 months after the treatment; 6. Eastern Cooperative Oncology Group (ECOG)performance status of 0-1; 7. Adequate organ function: 1. Bone marrow function: Hemoglobin count (HGB)≥80g/L; 2. Neutrophil count (NE)≥1.5×109/L; 3. White blood cell count (WBC)≥3.5×109/L; 4. Platelet count (PLT)≥100×109/L； 5. Liver function: i. Serum total bilirubin (TBIL)≤1.5×ULN; ii. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP)≤3×ULN, patients with liver metastasis≤5×ULN; 6. Kidney function: Blood creatinine (Cr) ≤1.5×ULN or Cockcroft Gault formula ≥ 60 mL/min; 7. Cardiac function: New York Heart Association (NYHA) classification140 mmHg or diastolic blood pressure>90 mmHg after treatment; 7. A history of arterial thrombosis or deep vein thrombosis within 6 months , or with evidence of bleeding tendency or medical history within 2 months, regardless of the severity; 8. Stroke event or transient ischemic attack occurred within 12 months. 3. Received systematic treatment with Chinese patent medicine or immunomodulatory drugs (including thymosin, interferon, interleukin, except for local use for ascites control) before the first administration within 2 weeks; 4. A history of interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis, acute lung disease, or systemic disease with poor control (including but not limited to diabetes, hypertension, etc.); 5. A history of active immune deficiency or autoimmune diseases, including HIV positive, or others acquired or congenital immune deficiency diseases, or organ transplantation; 6. Severe chronic or active infection requires systemic antibacterial, antifungal or antiviral treatment, including tuberculosis infection. A history of active tuberculosis infection ≥ 1 year should also be excluded, unless proved has been completed appropriate treatment; 7. Brain metastasis or leptomeningeal metastasis; 8. Clinically significant pleural effusion, pericardial effusion or ascites should be drained for many times within 2 weeks before the first administration of the drugs; 9. Another clinically detectable primary malignant tumor at the time of recruitment, or other malignant tumors in the past 5 years (except for fully treated skin basal cell carcinoma or cervical carcinoma in situ); 10. Any major surgery was performed ≤ 28 days before the drugs administration; 11. History of allogeneic stem cell transplantation or organ transplantation; 12. Be suffering gastrointestinal diseases: uodenal ulcer, ulcerative colitis, intestinal obstruction and others at present; or other conditions that may cause gastrointestinal bleeding or perforation judged by the researchers; or history of intestinal perforation or fistula, but has not recovered after surgical treatment; 13. Live vaccine are inoculated within 4 weeks (inclusive) before the first administration of the drugs, not including seasonal influenza vaccines but intranasal vaccine; 14. Other factors may lead to the forced termination of this trial according to the judgment of the investigator, such as other serious diseases (including psychological and mental diseases) requiring combined treatment, serious laboratory examination abnormalities, and family or social factors, which may affect the safety of the subject, or the collection of data and samples; 15. Participating in other therapeutic clinical studies or using research instruments within 4 weeks before the first administration; 16. Others conditions do not meet the inclusion according to the judgment of the investigator.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: The First Affiliated Hospital of Zhengzhou University

Address:
City: Zhengzhou
Zip: 450052
Country: China

Contact:
Last name: Yanru Qin, Doctor

Phone: 0371-66271157
Email: yanruqin@163.com

Contact backup:
Last name: Yongxu Jia, Doctor

Phone: 0371-66271156
Email: jiayongxu111@126.com

Start date: July 6, 2024

Completion date: July 6, 2027

Lead sponsor:
Agency: The First Affiliated Hospital of Zhengzhou University
Agency class: Other

Source: The First Affiliated Hospital of Zhengzhou University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06492317