SDH Gene MutationPhase 2PEMIGISTNCT07434843
PH 2 Pemigatinib in SDH-deficient GIST
A Phase 2 study testing Pemigatinib in people with SDH Gene Mutation and Gastrointestinal Stromal Tumor, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- SDH Gene Mutation, Gastrointestinal Stromal Tumor
- What is being tested?
- Pemigatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 19 May 2026to 1 Apr 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Suzanne George, MD, 877-338-7425
Suzanne George, MD
About this study
Official title: 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)
Read the 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.
- Conditions
- SDH Gene Mutation, Gastrointestinal Stromal Tumor
- Being tested
- Pemigatinib
- Keywords
- Gastrointestinal Stromal Tumor, Advanced SDH-deficient Gastrointestinal Stromal Tumor
- Medical subject headings
- Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PemigatinibDrug
Also called INCB054828
A selective Fibroblast Growth Factor Receptors inhibitor
- Tablet taken orally
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Pemigatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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.
Measured: 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.
Measured: From first dose of pemigatinib through 30 days after last dose of pemigatinib (approximately up to 36 months total on study time).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2026
- Study start19 May 2026
- Primary completion1 Oct 2028 (estimated)
- Study completion1 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SDH Gene MutationStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Gateway for Cancer Research, Incyte Corporation
- Responsible party
- Principal investigator, Suzanne George, MD, Dana-Farber Cancer Institute
- Investigators
- Suzanne George, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07434843
- Sponsor's protocol ID
- 25-666
- Acronym
- PEMIGIST
- Status last verified
- May 2026
- First submitted
- 29 Dec 2025
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PEMIGIST: Phase 2 Study of Pemigatinib (INCB054828) in the Treatment of Patients With Advanced SDH-deficient Gastrointestinal Stromal Tumor (GIST)
- ClinicalTrials.gov ID
- NCT07434843
- Acronym / sponsor ID
- PEMIGIST / 25-666
- Conditions
- SDH Gene Mutation, Gastrointestinal Stromal Tumor
- Keywords
- Gastrointestinal Stromal Tumor, Advanced SDH-deficient Gastrointestinal Stromal Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Gateway for Cancer Research, Incyte Corporation
- Study start
- 19 May 2026 (actual)
- Primary completion
- 1 Oct 2028 (estimated)
- Study completion
- 1 Apr 2029 (estimated)
- First posted
- 27 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PEMIGATINIB | Experimental | Drug: PemigatinibPemigatinib 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PemigatinibAlso: INCB054828A selective Fibroblast Growth Factor Receptors inhibitor * Tablet taken orally | Drug | PEMIGATINIB |
Primary outcome
Objective radiographic response rate
Time frame: From first dose of pemigatinib until the date of objective response per RECIST 1.1 through study completion, an average of 1 year
The objective response rate is defined as the rate of participants with a complete response or partial response, calculated using RECIST 1.1.
2 secondary outcomes
Progression-free survival (PFS)
Time frame: 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
Time frame: From first dose of pemigatinib through 30 days after last dose of pemigatinib (approximately up to 36 months total on study time).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Individual participant dataSharing planned: Yes. 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.
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RecruitingObservational study
Impact of Environmental Exposures on Tumor Risk in SDHx-mutation Carriers
SDH-Related Familial Paraganglioma, SDHx-Related Syndromes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Suzanne George, MD principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pemigatinib in people with SDH Gene Mutation and Gastrointestinal Stromal Tumor, run by Dana-Farber Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Suzanne George, MD (617-632-5204, suzanne_george@dfci.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective radiographic response rate (time frame: From first dose of pemigatinib until the date of objective response per RECIST 1.1 through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026; AzTrials last refreshed its copy on 1 Nov 2026.