Pemigatinib for FGF/FGFR Alterations Advanced Pan Solid Tumors

Inclusion Criteria:

1. Age ≥ 18 years old; Gender unlimited
2. Late stage, recurrent, or metastatic solid tumors confirmed by histology or cytologyas unresectable by surgery.
3. According to RECIST v1.1, there is at least one measurable lesion.
4. Histological confirmation of FGFR1-3 alterations, including but not limited toamplification, mutation, fusion/rearrangement, etc.
5. After standard treatment, the disease progresses, becomes intolerable, or standardtreatment is ineffective, or there is no standard treatment plan.
6. Has not previously used small molecule multi target inhibitors targeting the FGFRpathway (including arotinib, lenvatinib, sorafenib, apatinib, etc.).
7. ECOG physical fitness status is 0-1.
8. Expected survival time>3 months.
9. Sufficient organ function is required for the subject to meet the following laboratoryindicators:
10. In the past 14 days without using granulocyte colony stimulating factor, theabsolute value of neutrophils (ANC) ≥ 1.5x10^9/L.
11. Platelets ≥ 100 without blood transfusion in the past 14 days × 10^9/L.
12. In the absence of blood transfusion or use of erythropoietin within the past 14days, hemoglobin>9g/dL.
13. Total bilirubin ≤ 1.5 × Upper limit of normal value (ULN). Or total bilirubin>ULNbut direct bilirubin ≤ ULN.

5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are ≤ 2.5 × ULN (ALT or AST ≤ 5 allowed for patients with liver metastasis) × ULN).
6. Blood creatinine ≤ 1.5 × ULN and creatinine clearance rate (calculated usingCockcroft Fault formula) ≥ 50 ml/min.
7. Good coagulation function, defined as international standardized ratio (INR)or prothrombin time (PT) ≤ 1.5 times ULN. If the subject is undergoinganticoagulant therapy, as long as the PT is within the prescribed range ofanticoagulant drugs, it is sufficient.

10. For female subjects of childbearing age, they should undergo a urine or serumpregnancy test with a negative result within 3 days before receiving the first studydrug administration (day 1 of cycle 1). If the urine pregnancy test result cannot beconfirmed as negative, a blood pregnancy test is required. Non reproductive age womenare defined as those who have undergone at least one year of menopause or haveundergone surgical sterilization or hysterectomy.
11. If there is a risk of conception, all subjects (whether male or female) are requiredto use contraceptive measures with an annual failure rate of less than 1% throughoutthe entire treatment period until 120 days after the last study drug administration (or 180 days after the last chemotherapy drug administration).

Exclusion criteria:

1. Diagnosed within 5 years prior to the first administration as other malignant diseasesoutside of the current enrollment diagnosis (excluding basal cell carcinoma of theskin, squamous cell carcinoma of the skin, and/or carcinoma in situ after radicalresection).
2. Previously received selective FGFR inhibitor treatment.
3. Those who have received any other study drug treatment or participated in interventionclinical studies within 28 days before the first administration. Or receivedanti-tumor drug treatment (including Chinese herbal medicine with anti-tumorindications) within 28 days before the first use of the study drug.
4. Not fully recovered from toxicity and/or complications caused by any interventionmeasures before starting treatment (i.e. ≤ level 1 or reaching baseline, excludingfatigue or hair loss).
5. Symptomatic central nervous system metastasis and/or cancerous meningitis are known toexist. For brain metastasis subjects who have previously received treatment, if theircondition is stable (there is no evidence of imaging progression within at least 4weeks before the first administration of the trial treatment), repeated imagingexaminations confirm no evidence of new brain metastasis or enlargement of existingbrain metastasis lesions, and steroid treatment is not required at least 14 daysbefore the first administration of the trial treatment, they can participate in thetrial. This exception does not include cancerous meningitis, which should be excludedregardless of its clinical stability.
6. Known history of allogeneic organ transplantation and allogeneic hematopoietic stemcell transplantation.
7. The following laboratory parameters are abnormal:
8. Serum phosphate>ULN.
9. Serum calcium exceeds the normal range, or when serum albumin exceeds the normalrange, the corrected calcium concentration of serum albumin exceeds the normalrange.
10. Potassium level<lower limit of normal value. Potassium levels can be correctedthrough supplementation during screening.
11. Known history of human immunodeficiency virus (HIV) infection or confirmed positiveimmune test results.
12. Severe infections with active or poorly controlled clinical conditions.
13. Chest fluid, ascites, or pericardial effusion with obvious clinical symptoms thatrequire drainage treatment.
14. Individuals infected with acute or chronic active hepatitis B or hepatitis C, withhepatitis B virus (HBV) DNA>2000IU/ml or 10^4 copies/ml. Hepatitis C virus (HCV)RNA>10^3 copies/ml. Hepatitis B surface antigen (HbsAg) and anti HCV antibody werepositive at the same time. Those who have undergone nucleotides based antiviraltreatment and fall below the above standards can be enrolled in the group.
15. Clinically significant or uncontrolled heart diseases, including unstable anginapectoris, acute myocardial infarction occurring within 6 months prior to firstadministration, New York Heart Association Class III/IV congestive heart failure, anduncontrolled arrhythmia (allowing subjects with pacemakers or atrial fibrillation andgood heart rate control).
16. There are ECG changes or medical histories that researchers believe have clinicalsignificance. Screening QTcF interval>480 ms, for subjects with indoor conductionblock (QRS interval>120 ms), JTc interval can be used instead of QTc interval (if JTcis used instead of QTc, JTc must be ≤ 340 ms).
17. Uncontrolled hypertension, with systolic blood pressure>160 mmHg or diastolic bloodpressure>100 mmHg after optimal medical treatment, hypertension crisis or history ofhypertensive encephalopathy.
18. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh B grade or more severecirrhosis.
19. Has undergone major surgical procedures (craniotomy, thoracotomy, or laparotomy)within 4 weeks prior to the first dose of study treatment or is expected to requiremajor surgery during the study treatment period.
20. Toxicity and/or major surgical complications have not yet fully recovered beforestarting treatment.
21. Pregnant or lactating women, or subjects who are expected to conceive or give birthduring the study period from screening visits to completion of safety follow-up visits (male subjects up to 90 days after last administration).
22. Received radiotherapy within 4 weeks prior to the first administration of the studydrug. The radiation related toxicity of the subject must have fully recovered, andcorticosteroid treatment is not required. It is confirmed that radiation pneumonia hasbeen ruled out. For palliative radiotherapy for non-CNS diseases, a 2-week washoutperiod is allowed.
23. Have a history of systemic electrolyte metabolism imbalance caused by calcium andphosphorus metabolism disorders or accompanied by soft tissue ectopic calcification (excluding skin, kidney, tendon, or vascular calcification caused by injuries,diseases, and advanced age without systemic electrolyte metabolism imbalance).
24. Corneal or retinal diseases confirmed to have clinical significance through ophthalmicexamination.
25. Any potent CYP3A4 inhibitor (see Appendix A for details) or inducer has been usedwithin 14 days or 5 half-lives before the first administration of the study drug,whichever is shorter. Allow external use of ketoconazole.
26. It is known that there is an allergic reaction to Pemigatinib or its research drugexcipients.
27. Unable or unwilling to swallow Pemigatinib or suffering from significant digestivesystem diseases that may interfere with absorption, metabolism, or excretion.
28. The subject has a history of vitamin D deficiency and needs to supplement vitamin Dbeyond physiological levels (excluding vitamin D dietary supplements).
29. Other acute or chronic diseases, mental illnesses, or abnormal laboratory test valuesthat may lead to increased risk of study participation or drug administration, orinterference with the interpretation of study results, and the inclusion of patientsas ineligible to participate in this study based on the investigator's judgment.