Using toripalimab to treat advanced gastric cancer

Neoadjuvant Toripalimab in the Treatment of Locally Advanced dMMR/MSI-H Gastric or Gastroesophageal Junction Adenocarcinoma：an Open-label, Single-arm，Multi-center，Phase II Trial

This study is testing if a new drug called toripalimab can safely help people with advanced stomach cancer feel better and improve their treatment options.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, toripalimab
• Locations: 1 site (Guangzhou)
• Trial ID: NCT05994456 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the safety and efficacy of toripalimab, a PD-1 inhibitor, in patients with locally advanced dMMR/MSI-H gastric or gastroesophageal junction adenocarcinoma. Participants will receive toripalimab intravenously every three weeks, and their tumors will be assessed after two and four cycles of treatment. Based on the anti-tumor efficacy, patients may either proceed to surgery or withdraw from the study for routine treatment. The study aims to determine the tolerability of the drug and its potential to improve patient outcomes over a treatment period of up to two years.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with confirmed dMMR or MSI-H gastric or gastroesophageal junction adenocarcinoma and no distant metastasis.

Not a fit: Patients with non-dMMR or MSI-L gastric cancer or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced gastric cancer, potentially improving survival rates.

How similar studies have performed: Other studies using PD-1 inhibitors for similar conditions have shown promising results, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Aged 18-75 years, regardless of gender 2. Patients with histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction and confirmed dMMR or MSI-H 3. Preoperative CT or MRI staging meeting the following criteria: T2 and above, with or without lymph node involvement, without clear distant metastasis 4. ECOG score of 0-1. 5. Expected survival ≥ 2 years. 6. Good organ function (no blood transfusion, no hematopoietic stimulating factor, no albumin or blood product transfusion within 14 days prior to the examination).

1. Platelet (PLT) count ≥ 90\*109/L.
2. Neutrophil count (ANC) ≥ 1.5\*109/L.
3. Hemoglobin (Hb) level ≥ 9.0 g/dl.
4. International normalized ratio (INR) ≤ 1.5.
5. Prothrombin time (PT) and active partial thromboplastin time (APTT) ≤ 1.5 x ULN.
6. Glycated hemoglobin (HbA1c) \<7.5%.
7. Total bilirubin (TBIL) level ≤ 1.5 times the upper limit of normal (ULN).
8. Alanine amino transaminase (ALT) and aspartate amino transaminase (AST) levels ≤ 2.5 x ULN.
9. Serum creatinine (Cr) level ≤ 1.5 x ULN and creatinine clearance ≥ 60 ml/min.
10. Thyrotropin (TSH) ≤ ULN; serum free thyroid hormone (T4) normal; serum free triiodothyronine (T3) normal; (except for those who have received previous thyroid surgery or have a history of head and neck radiotherapy)
11. Serum amylase ≤ 1.5 x ULN.
12. Lipase ≤ 1.5×ULN. 7. Women of childbearing age must have a negative pregnancy test and must use contraception and avoid breastfeeding during the study and for 3 months after the last dose; male subjects must agree to use contraception during the study and for 3 months after the last dose.

8.Be able to understand and willing to sign a written informed consent form.

Exclusion Criteria:

1. Previously received chemotherapy, radiotherapy or immunotherapy for gastric cancer
2. Previously diagnosed any other malignancy with a primary site or histological type different from gastric cancer within 5 years prior to study entry, except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
3. With known hypersensitivity to the study drug or excipients, or to similar drugs
4. Received major surgery or open biopsy, or had a major trauma within 4 weeks prior to the start of study treatment
5. Received immunosuppressive drugs (excluding inhaled corticosteroids or ≤10 mg/day prednisone or equivalent pharmacophysiologic doses of other systemic steroids) within 2 weeks prior to the start of study treatment
6. Planned live attenuated vaccination within 4 weeks prior to the start of study treatment or during the study period
7. Inability to discontinue CYP3A4 inducers or inhibitors within 1 week prior to the start of study treatment and during the study period
8. Presence of any autoimmune disease or history of autoimmune disease.
9. Human immunodeficiency virus (HIV) infection (HIV antibody positive), or active hepatitis C virus (HCV) infection (HCV antibody positive), or active hepatitis B virus (HBV) infection (HBsAg positive and HBV-DNA ≥ 2000 IU/ml copies/ml)), or other serious infection requiring antibiotics for systemic therapy, or during screening/study Unexplained temperature \>38.5°C prior to the start of treatment.
10. Presence of the following diseases within 6 months prior to the start of study treatment: myocardial infarction, severe/unstable angina, NYHA class 2 or higher congestive heart failure, poorly controlled arrhythmias, etc.
11. Non-well-controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg under optimal treatment)
12. Arterial/venous thrombotic events such as cerebrovascular accidents (transient ischemic attack, cerebral hemorrhage, cerebral infarction, etc.), deep vein thrombosis, vasculitis, etc. within 3 months prior to the start of study treatment
13. Urine routine suggesting urine protein up to +++ and confirmed 24-hour urine protein quantification up to 1.0g.
14. The presence of a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation
15. Seizures requiring medication (e.g., steroids or antiepileptic drugs) for treatment.
16. Presence of a history of substance abuse, drug use, or alcohol dependence. Patients with other serious, acute or chronic medical conditions that may increase the risk of study participation and study medication, or that may interfere with the interpretation of study results, and who are judged by the investigator to be unsuitable for participation in a clinical trial.

Where this trial is running

Guangzhou

• Sun Yat-sen University Cancer Center — Guangzhou, China (Recruiting)

Study contacts

• Principal investigator: Dongsheng Zhang, PhD — Sun Yat-sen University
• Study coordinator: Dongsheng Zhang, PhD

Conditions Gastric or Gastroesophageal Junction Adenocarcinoma; dMMR/MSI-H; Gastric cancer