Using Pemigatinib to Treat Solid Tumors with FGFR Gene Alterations

Phase II Trial Evaluating the Efficacy of Pemigatinib in Patients With Recurrent and/or Metastatic Solid Tumor Harboring a FGFR Alteration

This study is testing if pemigatinib can help people with solid tumors that have FGFR gene changes, especially those with hard-to-treat cancers.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Unicancer (Academic / other)
• Drugs / interventions: pemigatinib, chemotherapy, immunotherapy, radiation
• Locations: 6 sites (Brest and 5 other locations)
• Trial ID: NCT06653777 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy of pemigatinib, an anti-cancer drug, in patients with solid tumors that have alterations in the FGFR gene. The study focuses on individuals with recurrent or metastatic cancers, excluding blood cancers, who have not found suitable alternative treatments. Participants will receive pemigatinib and will be closely monitored for disease control, including stabilization or reduction of cancer symptoms. The trial aims to gather data on the drug's effectiveness across various cancer types characterized by FGFR alterations.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed solid tumors that are locally recurrent, unresectable, or metastatic and have specific FGFR gene alterations.

Not a fit: Patients with blood cancers or those who have already been treated with pemigatinib may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with solid tumors harboring FGFR gene alterations.

How similar studies have performed: Other studies have shown promising results with FGFR inhibitors in various cancers, indicating potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed solid tumor
2. Patient with locally recurrent unresectable and/or advanced or metastatic disease harbouring a FGFR1,2,3 fusion/rearrangement or mutation
3. Age ≥ 18 years
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
5. Patient for whom there is no appropriate therapeutic alternative and for whom a FGFR inhibitor is indicated by the institution or the regional multidisciplinary consultation meeting and who may derive a benefit, according to the physician assessment
6. Estimated life expectancy \>3 months
7. Measurable disease according to response evaluation criteria in solid tumours version 1.1 (RECIST1.1), whatever the disease location. Tumor lesions located in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered measureable if progression has been clearly demonstrated in the lesion.
8. Availability of 2 pre-treatment tumor evaluations performed with an interval of at least 4 weeks and no more than 3 months between the examinations (CT or MRI, but same technics for both) and without any cancer treatment during this period
9. Patient with a minimal trend at 0.1 mm/day increase in tumor growth kinetics between pre-treatment and baseline scan, as assessed by the investigator
10. Adequate hematologic function: Absolute neutrophil count (ANC) \> 1.5 x 10⁹ /L; platelets \> 75 x 10⁹ /L; haemoglobin \> 9.0 g/dL. Transfusion is allowed with a 2-week washout period before treatment initiation
11. Adequate hepatic function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2,5 x upper limit of normal (ULN) (≤ 5 x ULN for liver metastasis); total bilirubin \< 1.5 x ULN (\< 2.5 x ULN if Gilbert's syndrome or liver metastasis); alkaline phosphatase (ALP) \< 3 x ULN
12. Adequate renal function: serum creatinine clearance \> 30 mL/minute based on Cockcroft-Gault formula
13. Value of serum phosphate ≤ ULN and value of serum calcium within institutional normal range (or serum albumin-corrected calcium within normal range when serum albumin is outside of the normal range)
14. Potassium levels within institutional normal range; supplementation can be used to correct potassium level during the screening.
15. Men, and women of childbearing potential must agree to use adequate contraception for the duration of trial participation and for at least one week after the last dose of pemigatinib. Men must also agree to not donate sperm and women must agree to not donate oocytes during the specified period
16. Women of childbearing potential must have a negative serum pregnancy test performed within 14 days before treatment initiation
17. Patient is affiliated to a social security system
18. Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in signing the patient's consent

Exclusion Criteria:

1. Hematologic malignancies
2. Known hypersensitivity or severe reaction to pemigatinib or excipients of pemigatinib
3. Patient with a disease and a FGFR alteration covered by a marketed indication for any selective FGFR inhibitor (e.g cholangiocarcinoma with FGFR2-fusion or a FGFR mutation are not eligible, while FGFR1 or 3 fusion are eligible)
4. Patient who received prior selective FGFR inhibitor
5. Patient who can be included in a recruiting study assessing FGFR inhibitor (including pemigatinib)
6. Current evidence of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination
7. Other current malignancy, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 5 years or more and are deemed at negligible risk for recurrence, are eligible for the trial
8. History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues such as skin, kidney tendon, or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance)
9. Significant gastrointestinal disorder(s) that could interfere with absorption, metabolism, or excretion of pemigatinib
10. Inability to swallow and retain oral medication
11. Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug/treatment administration, New York Heart Association Class III or IV congestive heart failure, and uncontrolled arrhythmia (participants with pacemaker or with atrial fibrillation and well-controlled heart rate are allowed)
12. History or presence of an abnormal electrocardiogram that, in the investigator's opinion, is clinically meaningful. A screening QTcF interval \> 480 ms is excluded.
13. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (defined as elevated transaminases or cirrhosis); chronic HBV/HCV infection with no cirrhosis and no elevated transaminases is allowed
14. Known HIV infection except if undetectable viral load
15. Other active chronic or current infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment within 2 weeks before enrollment (participants with asymptomatic chronic infections on prophylactic treatment are allowed)
16. Prior anticancer therapy, including radiotherapy, endocrine therapy, immunotherapy, chemotherapy or other investigational agents within the last 4 weeks (6 weeks for nitrosoureas and mitomycin C). A 1-week washout is permitted for palliative radiation to non-central nervous system disease. Patients must have recovered (≤ Grade 1) from AEs from previously administered therapies or local treatments before treatment initiation (excluding alopecia, anemia and decreased creatinine clearance)
17. Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or five half-lives (whichever is shorter) before the first dose of study drug
18. Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol
19. Inability or unlikeliness of the participant to comply with the dose schedule or with the medical evaluations and follow-up required by the trial because of geographic, familial, social, or psychological reasons
20. Women who are pregnant or breastfeeding
21. History of hypovitaminosis D requiring supraphysiologic doses (eg, 50,000 international unit (IU)/weekly) to replenish the deficiency.
22. Participation in another therapeutic trial within the 30 days prior to inclusion
23. Individuals deprived of liberty or placed under protective custody or guardianship

Where this trial is running

Brest and 5 other locations

• CHU de BREST — Brest, France (Recruiting)
• Centre Antoine Lacassagne — Nice, France (Active_not_recruiting)
• Institut Curie — Paris, France (Not_yet_recruiting)
• CHU Poitiers — Poitiers, France (Active_not_recruiting)
• CHU Saint Etienne — Saint-Priest-en-Jarez, France (Active_not_recruiting)
• Institut de Cancerologie de Lorraine — Vandœuvre-lès-Nancy, France (Active_not_recruiting)

Study contacts

• Principal investigator: Christophe LE TOURNEAU, Pr — Institut Curie Paris
• Study coordinator: Céline MAHIER AIT OUKHATAR

Conditions Solid Tumor, Miscellaneous; pemigatinib; FGFR alteration