PH 2 Pemigatinib in SDH-deficient GIST

Inclusion Criteria:

* Participant must have histologically confirmed SDH-deficient GIST. Participants must have locally advanced or metastatic disease that is not amenable to surgery.
* Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 12 (Measurement of Effect) for the evaluation of measurable disease.
* Participants must have radiographically documented progressive disease prior to study enrollment as per investigator assessment.
* Age ≥18 years
* ECOG performance status ≤2
* Participants must have adequate organ and marrow function as defined below:

  * Hemoglobin \> 8 g/dL. Patients with a hemoglobin of 7.5-8.0 g/dL may be eligible if the value is chronic, there is no clinical evidence of active bleeding, and eligibility is confirmed upon review and approval of the Sponsor-Investigator
  * Absolute neutrophil count ≥1,000/mcL
  * platelets ≥100,000/mcL
  * total bilirubin ≤1.5 × institutional upper limit of normal (ULN)
  * AST(SGOT)/ALT(SGPT) ≤3.0 × institutional ULN (unless liver metastases are present in which case it must be ≤ 5 × ULN)
  * glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 (using the CDK-EPI formula see Appendix B)
* Human immunodeficiency virus (HIV)-infected participants on effective non-CYP3A4 interacting (see Section 3.2.3) anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
* Participants must be disease-free of prior invasive malignancies for \> 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. NOTE: If there is a history of prior malignancy, participants must not be receiving other specific treatment for that cancer.
* Participants should have completed prior treatment for their cancer: chemotherapy or radiotherapy must have been completed for greater than 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
* Participants should have recovered from adverse events due to prior anti-cancer therapy (i.e.,have residual toxicities \> Grade 1) with the exception of alopecia.
* Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
* Participants must have a QTc interval length of below 450 msec. QTc will be calculated via the Fridericia's formula.
* Participant is willing to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
* Participant must be able to swallow and maintain pills.
* Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days of initial dose of pemigatinib (INCB054828), and again within 7 days prior to treatment on day 1. If screening occurs within 7 days of day 1, only one regnancy test is required.
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) and/or family member available will also be eligible.

Exclusion Criteria:

* Participants who are receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to pemigatinib (INCB054828).
* Concomitant administration with sensitive substrates/narrow therapeutic index drugs of CYP3A4, P-gp BCRP, MATE1, and MATE2K, and strong inhibitors and inducers of CYP3A4 should be avoided. Use caution with strong inhibitors and inducers of P-gp. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product. (See Appendix C Participant Drug Information Handout and Wallet Card).
* Participants with uncontrolled intercurrent illness.
* Participants with psychiatric illness/social situations that would limit compliance with study requirements.
* Women of childbearing potential unwilling or unable to perform contraception from screening until 4 months after completion of pemigatinib administration
* Men unwilling or unable to perform contraception from screening to until 4 months after completion of pemigatinib administration.
* Participants previously treated with a FGFR inhibitor.
* History of hypovitaminosis D requiring supraphysiologic doses (e.g., 50,000 UI/weekly or above). Vitamin D supplements are allowed.
* Participants with calcium and phosphate levels exceeding the upper limit of normal (ULN) despite medical intervention within 2 weeks prior to the first dose of pemigatinib.
* Current evidence of corneal or retinal abnormalities that may increase eye toxicity, including but not limited to:

  * Currently suffering from central serous retinopathy (CSR) or retinal vein occlusion (RVO), or with relevant history
  * Active wet age-related macular degeneration (wAMD)
  * Diabetic retinopathy with macular edema
  * Uncontrollable glaucoma
  * Keratopathy, such as keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflammation or ulceration
* Treatment with any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug.
* Participants with a history of soft tissue calcifications on imaging that are associated with documented abnormalities in calcium or phosphate levels except for soft tissue calcification due to aging, previous injury or other disease