Pemigatinib for the Treatment of Locally Advanced or Metastatic SDH-Deficient Gastrointestinal Stromal Tumors, PEMIGIST Trial
This phase II trial studies how well pemigatinib works in treating patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors that have spread to nearby tissue or lymph nodes (locally advanced) or that have spread from where they first started (primary site) to other places in the body (metastatic). Pemigatinib works by targeting specific proteins called fibroblast growth factor receptors (FGFRs), which contribute to the growth and survival of tumor cells. Blocking FGFR activity can help slow down or stop the growth of tumor cells that rely on these proteins for survival.
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
- Participants must have radiographically documented progressive disease prior to study enrollment as per investigator assessment
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- 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)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [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 m^2 (using the Chronic Kidney Disease Epidemiology Collaboration [CDK-EPI] formula)
- Human immunodeficiency virus (HIV)-infected participants on effective non-CYP3A4 interacting 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 corrected QT (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 pregnancy 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
- 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 sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07434843.
Locations matching your search criteria
United States
Massachusetts
Boston
PRIMARY OBJECTIVE:
I. To estimate the objective radiographic response rate to single agent pemigatinib (INCB054828) in participants with advanced SDH-deficient gastrointestinal stromal tumor (GIST).
SECONDARY OBJECTIVES:
I. To estimate progression-free survival (PFS) in participants with SDH-deficient GIST treated with pemigatinib (INCB054828).
II. To assess safety and tolerability of pemigatinib (INCB054828) as measured by the frequency, severity, and attribution of adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria.
EXPLORATORY OBJECTIVES:
I. To explore the relationship between somatic genomic alterations, as determined by standard of care tumor genomic sequencing, including SDH-X alterations and response to pemigatinib (INCB054828).
II. To explore the relationship between germline alterations in SDH-X, as determined by standard of care germline sequencing, and response to pemigatinib (INCB054828).
OUTLINE:
Patients receive pemigatinib orally (PO) once daily (QD) on days 1-14 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo optical coherence tomography (OCT) and computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) throughout the study. Patients may also undergo archival tissue sample collection on study.
After completion of study treatment, patients are followed up at 30 days.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorSuzanne George
- Primary ID25-666
- Secondary IDsNCI-2026-02184
- ClinicalTrials.gov IDNCT07434843