This prospective phase Il study is aim to evaluate the efficacy and safety of FGFR inhibitor combined with immune checkpoint inhibitors in FGFR1/2/3 variant advanced solid tumors.

Inclusion Criteria:

• Age ≥ 18 years;

• Histologically or cytologically confirmed unresectable advanced solid tumors with failure or intolerance to standard treatments;

• At least one measurable lesion per RECIST v1.1 criteria;

• Gene testing confirms FGFR1/2/3 variants, including but not limited to mutations, fusions/rearrangements in solid tumors;

• Patients have not previously used specific small molecule multi-target inhibitors of the FGFR pathway, as assessed by investigators, and have been treated with immune checkpoint inhibitors;

• ECOG performance status of 0-1;

• Expected survival time > 3 months;

• Laboratory criteria:

  1. Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L in the past 14 days without granulocyte colony-stimulating factor;
  2. Platelets ≥ 100 x 10⁹/L without transfusion in the past 14 days;
  3. Hemoglobin > 9 g/dL in the last 14 days without transfusion or erythropoietin;
  4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN), or total bilirubin > ULN but direct bilirubin ≤ ULN;
  5. AST, ALT ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver metastasis);
  6. Serum creatinine ≤ 1.5 x ULN and creatinine clearance (Cockcroft-Gault) ≥ 50 ml/min;
  7. Good coagulation function, defined as INR or PT ≤ 1.5 x ULN. If on anticoagulant therapy, PT should be within the therapeutic range of anticoagulants;

• Female subjects of reproductive age must have a negative urine or serum pregnancy test within 3 days prior to the first dose (Cycle 1, Day 1). If the urine test is inconclusive, a blood test is required. Non-reproductive females are defined as post-menopausal for at least one year or surgically sterile;

• Subjects with reproductive potential must use contraception with an annual failure rate of less than 1% during treatment and for 120 days after the last study drug dose (or 180 days after the last chemotherapy dose).

Exclusion Criteria:

• Diagnosis of other malignancies within 3 years before the first dose, except for certain treated skin carcinomas and in-situ carcinomas;

• Previous treatment with selective FGFR inhibitors;

• Receipt of other investigational drugs within 21 days or antitumor drugs within 14 days before the first dose;

• Unresolved toxicity from prior treatments unless ≤ Grade 1 or related to alopecia or fatigue;

• Known symptomatic CNS metastasis or carcinomatous meningitis. Stable patients post-treatment with no evidence of progression may be eligible if steroid-free for at least 14 days;

• History of allogeneic organ or hematopoietic stem cell transplantation;

• Abnormal laboratory parameters:

  1. Serum phosphate > 1.5 x ULN;
  2. Elevated serum calcium or albumin-adjusted calcium outside the reference range;

• Known HIV infection or positive HIV test;

• Active or poorly controlled serious infection;

• Need for drainage treatment for pleural effusion, ascites, or pericardial effusion;

• Active hepatitis B or C infection with high viral load, or positive HBsAg or anti-HCV antibodies. Patients on antiviral therapy must meet lower thresholds;

• Significant uncontrolled heart disease, including recent MI, severe heart failure, or uncontrolled arrhythmias;

• Clinically significant ECG changes or history of significant cardiac issues; Screening QTcF interval > 480 ms, or JTc interval if applicable, must be ≤ 340 ms;

• Uncontrolled hypertension despite treatment;

• Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh grade B or higher cirrhosis;

• Major surgery within 4 weeks before the first dose or planned major surgery during the study;

• Unresolved complications from prior surgery;

• Pregnant or breastfeeding women, or those planning to become pregnant during the study period and for safety follow-up;

• Radiotherapy within 4 weeks before the first dose, except for non-CNS palliative radiotherapy with a 2-week washout period;

• History of systemic electrolyte imbalance or ectopic soft tissue calcification;

• Clinically significant corneal or retinal disease;

• Use of potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives before the first dose;