Pemigatinib for Gastrointestinal Stromal Tumor

(PEMIGIST Trial)

Overseen By Suzanne George, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Uncontrolled illness, Psychiatric illness, FGFR inhibitor, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 23

Duration: Up to 36 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pemigatinib, a drug, to evaluate its effectiveness in treating gastrointestinal stromal tumors (GIST) that lack the enzyme SDH. The study examines the drug's efficacy and potential side effects. It suits individuals with advanced or metastatic GIST that cannot be surgically removed and have recently worsened. Participants will take the medication daily for two weeks, followed by a week off, in repeated cycles. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Is there any evidence suggesting that pemigatinib is likely to be safe for humans?

Previous studies have shown pemigatinib to be generally safe. Research indicates that most patients tolerate this drug well, with many experiencing manageable side effects. Common side effects include mild swelling, dry eyes, and fatigue. Serious side effects are rare but can occur, such as changes in liver function, which doctors monitor closely with blood tests.

Pemigatinib has also been studied for conditions like cholangiocarcinoma (a type of bile duct cancer), where it demonstrated a good safety record. Although the FDA has not approved pemigatinib specifically for gastrointestinal stromal tumors (GIST), its use in treating other conditions suggests it is relatively safe for patients. Always consult a healthcare provider to understand the risks and benefits for your situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for GIST?

Pemigatinib is unique because it targets specific genetic mutations in cancer cells, known as FGFR mutations, which are not addressed by current treatments for gastrointestinal stromal tumors (GIST). Most GIST treatments, like imatinib, work by inhibiting the KIT or PDGFRA enzymes, but pemigatinib offers a new approach by focusing on a different pathway. This targeted action could provide an effective option for patients whose tumors have developed resistance to existing therapies, making researchers hopeful about its potential to improve outcomes.

What evidence suggests that pemigatinib might be an effective treatment for gastrointestinal stromal tumors?

Research has shown that pemigatinib, the investigational treatment in this trial, might help treat gastrointestinal stromal tumors (GIST) that resist other treatments. This is particularly true for tumors with changes in the FGFR2 gene, which do not respond well to standard treatments like imatinib. In other cancers with similar genetic changes, such as intrahepatic cholangiocarcinoma, pemigatinib has extended the time patients live without cancer progression, typically for about 6–7 months. This suggests that targeting similar pathways in GIST with pemigatinib could be beneficial. By blocking certain signals in the cancer cells, pemigatinib may slow or halt tumor growth. ^{1 2 6 7 8}

Who Is on the Research Team?

Suzanne George, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Inclusion Criteria

Participant must have measurable disease as per defined criteria

I have HIV, my viral load is undetectable, and my treatment does not interact with CYP3A4.

I have recovered from side effects of my previous cancer treatment.

Exclusion Criteria

Participants receiving any other investigational agents

History of allergic reactions to compounds similar to pemigatinib

I am not taking any drugs that should not be used with this treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive oral pemigatinib continuously in 21-day cycles until disease progression or unacceptable toxicity

Up to 36 months

In-clinic visits every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Pemigatinib

How Is the Trial Designed?

Group I: PEMIGATINIB Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12564403/

Molecular Mechanisms and Clinical Implications of Fibroblast ...

FGFR2-altered GISTs exhibit primary refractoriness to imatinib (median PFS 1.9 months) versus KIT exon 11 mutants (median PFS 24.7 months).

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S0923753425007410

Twenty-year survival of advanced gastrointestinal stromal ...

With >18 years of median follow-up, imatinib provides 20-year survival for >10% of patients with advanced GIST. •. GIST with KIT exon 11 mutations, female sex, ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07434843

NCT07434843 | PH 2 Pemigatinib in SDH-deficient 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 ...

4.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2822397

Incidence and Survival Outcomes of Gastrointestinal ...

In this study, we evaluated recent GIST incidence trends and survival outcomes by race and ethnicity using data from the National Cancer ...

5.

onco-hema.healthbooktimes.org

onco-hema.healthbooktimes.org/article/90103-evolving-therapeutic-strategies-in-gastrointestinal-stromal-tumors

Evolving Therapeutic Strategies in Gastrointestinal Stromal ...

When localized and operable, GISTs have a favorable prognosis with a five-year overall survival of around 80%. In the metastatic setting, the ...

6.

jgo.amegroups.org

jgo.amegroups.org/article/view/99315/html

Safety and efficacy of pemigatinib in patients with ...

This systematic review suggests that pemigatinib has modest therapeutic efficacy in CCA patients, with a considerable proportion achieving disease control.

7.

dana-farber.org

dana-farber.org/clinical-trials/25-666

PEMIGIST: Phase 2 Study of Pemigatinib (INCB054828) in ...

The purpose of this study is to determine how effective the drug pemigatinib is as a treatment option for advanced succinate dehydrogenase (SDH)-deficient ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12365427/

Safety profiles of the new target therapies—pemigatinib ... - PMC

A high mortality rate is reported for CCA due to its rapid progression, late diagnosis, and resistance mechanisms related to immunoregulatory ...