Rare Pancreas cancer FGFR + KRAS trial - comes to you
- Terri Conneran KRAS Kickers
- May 19
- 6 min read
Updated: Jun 10
A Phase II Telemedicine Study of Pemigatinib in Adult Patients With Advanced or Metastatic Pancreas Cancer With FGFR Genetic Alterations
The Ohio State University Comprehensive Cancer Center
fully decentralized clinical trial model!
A new Phase II decentralized telemedicine trial is underway to evaluate pemigatinib (Pemazyre) in adults with advanced or metastatic pancreatic cancer harboring FGFR (fibroblast growth factor receptor) genetic alterations. This study is particularly notable for its decentralized design, allowing patients across the U.S. to participate remotely, minimizing the need for travel .
FGFR alterations, though rare in pancreatic ductal adenocarcinoma (PDAC), represent actionable targets. Pemigatinib, an oral FGFR1–3 inhibitor, has demonstrated efficacy in other FGFR-driven cancers, such as cholangiocarcinoma . The decentralized design aims to increase accessibility for patients who might otherwise face barriers to participation due to geographic or logistical constraints .
Phase II trial, OSUCCC researchers will investigate whether the drug could also be effective for pancreatic cancer patients with different types of FGFR alterations.
Enrollment Goal: 40 patients
Design: Single-arm, open-label, decentralized (telemedicine-based)
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. Patients also undergo blood sample collection, computed tomography (CT) and/or magnetic resonance imaging (MRI), and optical coherence tomography (OCT) throughout the study. Patients may also undergo whole body bone scans and dilated fundoscopy as clinically indicated. After completion of study treatment, patients are followed up at 30 days, then every 4 months for one year.
PRIMARY OBJECTIVES:
I. To evaluate the efficacy of single agent pemigatinib in patients with advanced or metastatic pancreas cancer of any histologic classification with FGFR2 gene fusions/translocations.
II. To understand response rate and potential for pemigatinib to benefit patients who have other FGFR alterations including point mutations, extracellular small indels and kinase domain duplications in pancreas cancer.
SECONDARY OBJECTIVES:
I. To further evaluate the efficacy of single agent pemigatinib in each above cohort separately.
II. To characterize the safety and tolerability of single agent pemigatinib.
Inclusion Criteria
Patients with histologically or cytologically confirmed advanced or metastatic pancreatic cancer of any histologic classification at the time of diagnosis
Written documentation of local or central Clinical Laboratory Improvement Act (CLIA)-certified laboratory determination of FGFR gene fusions/translocations or activating mutations
The study is open to pancreatic cancer in the following cohorts:
Cohort 1: Pancreatic cancer of any histology with FGFR2 fusion/translocation (n, up to 30) who have progressed on or are intolerant to at least one standard of care (SOC) therapy. Prior therapy with a different FGFR inhibitor is not permitted. Patients with concurrent Kirsten rat sarcoma (KRAS) mutations are excluded from this cohort
Cohort 2: Pancreatic cancer of any histology with activating point mutations, fusion/translocation (FGFR1,3,4) extracellular small indels, or kinase domain duplications (n, up to 10). Patients must have progressed on or are intolerant to at least one SOC therapy. Prior therapy with a different FGFR inhibitor is not permitted. Patients with concurrent KRAS mutations are permitted in this cohort
Evidence of measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Patients must have received at least one prior SOC regimen for advanced/metastatic pancreas cancer. Patients should have had evidence of progressive disease following their prior regimen, or if prior treatment was discontinued due to toxicity must have continued evidence of measurable or evaluable disease. Patients who have received prior treatment with an alternate FGFR inhibitor are not eligible for the study
Patients with symptomatic central nervous system (CNS) metastases are excluded (because it is unclear how much CNS penetration the drug has). However, asymptomatic patients with history of successfully treated CNS metastases with surgery or radiation and follow up imaging showing stability, can be eligible
Patients ≥ 18 years of age of either gender
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (patients with ECOG performance status of 2 may be considered on a case-by-case basis after discussion with Incyte)
Able to read and/or understand the details of the study and provide written evidence of informed consent as approved by Institutional Review Board (IRB)/Ethics Committee (EC)
Recovery from adverse events of previous systemic anti-cancer therapies to baseline or Grade 1, except for:
Alopecia
Stable neuropathy of ≤ Grade 2 due to prior cancer therapy
Able to swallow and retain oral medication
Willing and able to comply with scheduled visits, treatment plan and laboratory tests
Exclusion Criteria
Neurological symptoms related to underlying disease requiring increasing doses of corticosteroids.
* Note: Steroid use for management of CNS tumors is allowed but must be at a stable dose for at least 2 weeks preceding study entry
History of another primary malignancy except adequately treated in situ carcinoma of the cervix or non-melanoma carcinoma of the skin or any other curatively treated malignancy that is not expected to require treatment for recurrence during the course of the study or affect survival
Any other medical condition that would, in the investigator's , prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures
Current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjuctivitis, confirmed by ophthalmologic examination
History and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral pemigatinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc.
Treatment with any of the following anti-cancer therapies prior to the first dose of pemigatinib within the stated timeframes:
Cyclical chemotherapy (intravenous) within a period of time that is shorter than the cycle length used for that treatment (e.g., 6 weeks for nitrosourea, mitomycin-C)
Biological therapy (e.g., antibodies - including bevacizumab) within a period of time that is ≤ 5 t1/2 or ≤ 4 weeks, whichever is shorter, prior to starting study drug
Continuous or intermittent small molecule therapeutics within a period of time that is ≤ 5 t1/2 or ≤ 4 weeks (whichever is shorter) prior to starting study drug
Any other investigational agents within a period of time that is ≤ 5 t1/2 or less than the cycle length used for that treatment or ≤ 4 weeks (whichever is shortest) prior to starting study drug
Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug
Patients who are currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration are excluded. Patients are not permitted to receive enzyme-inducing anti-epileptic drugs
Consumption of grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges or products within 7 days prior to first dose
Absolute neutrophil count (ANC) ≤ 1,000/mm^3 [1.0 x 10^9/L]
Platelets ≤ 75,000/mm^3 [75 x 10^9/L] • Hemoglobin ≤ 9.0 g/dL
Total bilirubin ≥ 1.5x upper limit of normal (ULN) unless associated with patient's primary cancer and/or metastases and with principal investigator's approval
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 3x ULN unless associated with patient's primary cancer and/or metastases and with principal investigator's approval
Alkaline phosphatase ≥ 2.5x ULN unless associated with patient's primary cancer and/or metastases and with principal investigator's approval
Calculated or measured creatinine clearance of < 40 mL/min
Calcium-phosphate homeostasis:
Inorganic phosphorus outside of institutional normal limits
Total serum calcium (can be corrected) outside of institutional normal limits
History of clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction, New York Heart Association Class III or IV congestive heart failure, or arrhythmia requiring therapy. Subjects with a pacemaker and well-controlled rhythm for at least 1 month prior to first dose will be allowed
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months following the discontinuation of study treatment. Highly effective contraception methods include:
ClinicalTrials.gov ID NCT06906562
Sponsor Sameek Roychowdhury
Information provided by Sameek Roychowdhury, Ohio State University Comprehensive Cancer Center (Responsible Party)
Last Update Posted 2025-05-11
The US Food and Drug Administration a few years ago approved Pemazyre, an FGFR1/2/3 inhibitor, for patients with previously treated, unresectable or metastatic bile duct cancer with FGFR2 fusions or other rearrangements. The drug also treats relapsed or refractory myeloid/lymphoid neoplasms with an FGFR1 rearrangement.i
In the FIGHT-207 basket trial, pemigatinib showed activity across various FGFR-altered tumors, including pancreatic cancer. Notably, a patient with FGFR1–PDE4DIP fusion-positive pancreatic cancer experienced disease progression due to acquired resistance mutations, highlighting both the potential and challenges of FGFR-targeted therapies in this context .