Ivarmacitinib in Advanced Solid Tumors: A Prospective, Two-Cohort, Two-Phase Exploratory Study in Patients Discontinued Due to Immune Intolerance

Inclusion Criteria

• •1. Age ≥ 18 years.
• •2. ECOG performance status score 0-1.
• •3. Expected survival ≥ 12 weeks.
• •4. Solid tumor patients who have discontinued treatment with immune checkpoint inhibitors (ICIs).
• •5. Treatment with ICIs may be administered as monotherapy or in combination with other therapies (including but not limited to radiotherapy, chemotherapy, targeted therapy, etc.).
• •6. Current Status of irAE:
• •Cohort I:
• •1. Patients currently diagnosed with steroid-resistant or steroid-dependent immune-related adverse events (immune myocarditis, immune colitis, immune myositis-arthritis, immune skin reactions, immune hepatitis, etc.);
• •2. Patients with contraindications to steroid use, or who refuse continued steroid therapy due to adverse reactions following steroid administration.
• •Cohort II:
• •1. Patients discontinued immunotherapy due to irAE (CTCAE 5.0) after receiving ≥1 line of treatment including ICIs;
• •2. Time since discontinuation of immunotherapy due to irAE ≤3 months;
• •3. irAE has resolved to ≤Grade 1.
• •7. The patient still possesses certain organ and bone marrow functions:
• •Cohort 1:
• •1. Hemoglobin ≥90 g/L, neutrophil count ≥1.0 × 10\^9/L, platelet count ≥75 × 10\^9/L; lymphocyte count ≥0.5 × 10\^9/L; coagulation function: INR, APTT, and PT all ≤1.5 × UNL;
• •2. Liver function: Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 3 × ULN, alanine aminotransferase (ALT) ≤ 3 × ULN. For patients with immune hepatitis, specific liver function biochemical parameters are not restricted; adequate liver function is defined as Child-Pugh class A-B;
• •3. Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min;
• •4. Or patients assessed by the investigator as having adequate organ function.
• •Cohort II:
• •Organ function levels must meet the following requirements (no blood transfusion or hematopoietic growth factor therapy within 2 weeks prior to blood screening):
• •1. ANC ≥ 1.5 × 10⁹/L;
• •2. PLT ≥ 100 × 10⁹/L;
• •3. Hb ≥ 90 g/L;
• •4. TBIL ≤ 1.0 × ULN;
• •5. ALT and AST ≤ 2.5 × ULN;
• •6. BUN and Cr ≤ 1.5 × ULN.
• •8. All women of childbearing potential must have a negative serum pregnancy test during the screening period and must use reliable contraception from signing the informed consent form until 3 months after the last dose.
• •9. Subjects voluntarily participate in this study, sign the informed consent form prior to the screening process, demonstrate good compliance, and cooperate with safety follow-up.
• •10. The subject is judged by the investigator to be able to adhere to the study protocol.