PH 2 Pemigatinib in SDH-deficient GIST

NCT07434843 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-666
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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)

Conditions

SDH Gene Mutation; Gastrointestinal Stromal Tumor

Keywords

Gastrointestinal Stromal Tumor; Advanced SDH-deficient Gastrointestinal Stromal Tumor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Progression-free survival (PFS)

  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

  From first dose of pemigatinib through 30 days after last dose of pemigatinib (approximately up to 36 months total on study time).

Study Arms (1)

PEMIGATINIB

EXPERIMENTAL

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

Interventions

Pemigatinib DRUG

A selective Fibroblast Growth Factor Receptors inhibitor * Tablet taken orally

Also known as: INCB054828

PEMIGATINIB

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Gateway for Cancer Research: collaborator
• Incyte Corporation: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

pemigatinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Study Officials

• Suzanne George, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Suzanne George, MD

CONTACT

617-632-5204; suzanne_george@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 29, 2025
• First Posted: February 27, 2026
• Study Start: May 19, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): April 1, 2029
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)