PH 2 Pemigatinib in SDH-deficient GIST (PEMIGIST)

PEMIGIST: Phase 2 Study of Pemigatinib (INCB054828) in the Treatment of Patients With Advanced SDH-deficient Gastrointestinal Stromal Tumor (GIST)

The purpose of this study is to determine how effective the drug pemigatinib is as a treatment option for advanced succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors(GIST). This study will also assess the side effects associated with pemigatinib and evaluate its tolerability.

The name of the study drug involved in this study is:

• Pemigatinib (INCB054828)

Study Overview

• Status: Recruiting
• Conditions: Gastrointestinal Stromal Tumor; SDH Gene Mutation
• Intervention / Treatment: Drug: Pemigatinib

Detailed Description

This is a single-arm, open-label Phase 2 trial evaluating the clinical efficacy of pemigatinib (INCB054828) in patients with advanced succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors.

The U.S. Food and Drug Administration (FDA) has not approved pemigatinib for advanced succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors but it has been approved for other uses.

The research study procedures include screening for eligibility, study treatment in-clinic visits, physical exam, routine blood tests, pregnancy test, Electrocardiogram (ECG),Imaging Scans, Tumor sample, Data and biological specimen collection.

Eligible participants will receive oral pemigatinib (INCB054828) continuously in 21-day cycles until disease progression or unacceptable toxicity. Follow up will begin 30 days after treatment stops.

It is expected that about 24 people will take part in this research study.

Incyte, a biopharmaceutical company, is supporting this research study by providing the study drug.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Suzanne George, MD; Phone Number: 617-632-5204; Email: suzanne_george@dfci.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Principal Investigator: Suzanne George, MD
      • Contact: Suzanne George, MD; Phone Number: 877-338-7425

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PEMIGATINIB; Pemigatinib will be taken orally 1x daily on Days 1-14, not taken days 15-21 of each 21-day study cycle (2 weeks on, 1 week off). Cycles will continue until disease progression, unacceptable toxicity, or other protocol-defined criteria	Drug: Pemigatinib; A selective Fibroblast Growth Factor Receptors inhibitor; Tablet taken orally; Other Names: INCB054828

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective radiographic response rate	The objective response rate is defined as the rate of participants with a complete response or partial response, calculated using RECIST 1.1.	From first dose of pemigatinib until the date of objective response per RECIST 1.1 through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-Free Survival (PFS) based on the Kaplan-Meier method is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at the earliest date of last disease evaluation or off treatment date.	Participants alive without disease progression are censored at the earliest date of last disease evaluation or off treatment date] average of 2yrs.
Incidence of Grade 3 or Higher Treatment-Related Toxicity	Number and proportion of participants experiencing at least one Grade 3, 4, or 5 treatment related adverse event, as defined and graded by NCI CTCAE v5.0. Events will be summarized overall and by type of event.	From first dose of pemigatinib through 30 days after last dose of pemigatinib (approximately up to 36 months total on study time).

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Incyte Corporation; Gateway for Cancer Research
• Investigators: Principal Investigator: Suzanne George, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: December 29, 2025
• First Submitted That Met QC Criteria: February 22, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Gastrointestinal Stromal Tumor; Advanced SDH-deficient Gastrointestinal Stromal Tumor
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; pemigatinib
• Other Study ID Numbers: 25-666

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes