Status:

NOT_YET_RECRUITING

Pemigatinib and Immune Checkpoint Inhibitor Treated FGFR1/2/3 Alteration Advanced Solid Tumor

Lead Sponsor:

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Conditions:

Urothelial Carcinoma

Breast Neoplasms

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

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.

Eligibility Criteria

Inclusion

  • 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:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L in the past 14 days without granulocyte colony-stimulating factor;
  • Platelets ≥ 100 x 10⁹/L without transfusion in the past 14 days;
  • Hemoglobin \> 9 g/dL in the last 14 days without transfusion or erythropoietin;
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN), or total bilirubin \> ULN but direct bilirubin ≤ ULN;
  • AST, ALT ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver metastasis);
  • Serum creatinine ≤ 1.5 x ULN and creatinine clearance (Cockcroft-Gault) ≥ 50 ml/min;
  • 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

  • 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:
  • Serum phosphate \> 1.5 x ULN;
  • 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;

Key Trial Info

Start Date :

August 15 2024

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

December 31 2026

Estimated Enrollment :

30 Patients enrolled

Trial Details

Trial ID

NCT06551896

Start Date

August 15 2024

End Date

December 31 2026

Last Update

August 13 2024

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