Efficacy of Pemigatinib in Patients With Solid Tumors Characterized by an Alteration of the Gene FGFR in Tumor Cells

NCT06653777 | Recruiting Phase 2 DMC

• 2 other identifiers: UC-GMP-23052024-512729-10-00
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

Brief Summary

Alterations in the fibroblast growth factor receptor (FGFR) gene are involved in the development of cancer. These anomalies are found at very variable frequencies (from less than 1% to around 10%) in cancers of the bile ducts, bladder, uterus, brain, ovary, lung, airways, digestive tract, breast, etc. Pemigatinib is an anti-cancer drug that acts on cells with alterations in the FGFR gene. It is used in Europe to treat people with biliary tract cancer who carry a specific FGFR alteration. However, in various clinical trials, pemigatinib has shown interesting activity in a number of patients with different cancers presenting with an alteration in the FGFR gene. This treatment could therefore be effective in several types of cancer where an alteration in the FGFR gene is detected. The aim of this clinical trial is to learn if pemigatinib works to treat patients with recurrent and/or metastatic cancer (whatever the type of cancer excluding blood cancers and those already treated with pemigatinib) presenting an alteration in the FGFR gene. Patients will:

• Take oral pemigatinig in 3-week cycles (every day for 2 weeks followed by one week without pemigatinib) as long as they benefit from it.
• Visit the clinic once every 3 weeks for checkups and tests during the treatment period
• Visit the clinic once every 3 months for checkups after stopping treatment for at least 12 months.

Conditions

Solid Tumor, Miscellaneous

Keywords

pemigatinib; FGFR alteration

Outcome Measures

Primary Outcomes (1)

• Tumor regression

  Proportion of patients experiencing an objective response or at least a 30% decrease in tumor growth kinetics at disease progression on study treatment as compared to the one calculated from the two pre-treatment tumor evaluations. The tumor kinetics variation is measured by the tumor growth ratio defined as the ratio of the slope of tumor growth on treatment (between the nadir and disease progression) and the slope of tumor growth before treatment. The sum of the diameters of target lesions according to RECIST 1.1 will be calculated on each patient's imaging by the Blinded Independent Central Review (BICR).

  From enrollment to disease progression, up to 42 months

Secondary Outcomes (8)

• Overall response rate (ORR)

  From enrollment to the progression, up to 42 months

• Clinical benefit rate (CBR)

  From enrollment to the progression, up to 42 months

• Duration of response (DoR)

  From enrollment to the progression, up to 42 months

• Progression-free survival (PFS)

  From enrollment to disease progression or death, up to 42 months

• Time to treatment failure (TTF)

  From enrollment to the end of treatment (or up to 42 months)

Study Arms (1)

pemigatinib

EXPERIMENTAL

Pemigatinib will be administered orally once daily for 2 weeks followed by a 1-week off (intermittent schedule 2/1).

Drug: Pemigatinib

Interventions

Pemigatinib DRUG

Pemigatinib will be administered orally once daily for 2 weeks followed by a 1-week off (intermittent schedule 2/1).

Also known as: Pemazyre®

pemigatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed solid tumor
• Patient with locally recurrent unresectable and/or advanced or metastatic disease harbouring a FGFR1,2,3 fusion/rearrangement or mutation
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• 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
• Estimated life expectancy \>3 months
• 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.
• 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
• 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
• 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
• 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
• Adequate renal function: serum creatinine clearance \> 30 mL/minute based on Cockcroft-Gault formula
• 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)
• Potassium levels within institutional normal range; supplementation can be used to correct potassium level during the screening.
• 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

You may not qualify if:

• Hematologic malignancies
• Known hypersensitivity or severe reaction to pemigatinib or excipients of pemigatinib
• 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)
• Patient who received prior selective FGFR inhibitor
• Patient who can be included in a recruiting study assessing FGFR inhibitor (including pemigatinib)
• Current evidence of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination
• 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
• 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)
• Significant gastrointestinal disorder(s) that could interfere with absorption, metabolism, or excretion of pemigatinib
• Inability to swallow and retain oral medication
• 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)
• History or presence of an abnormal electrocardiogram that, in the investigator's opinion, is clinically meaningful. A screening QTcF interval \> 480 ms is excluded.
• 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
• Known HIV infection except if undetectable viral load
• 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)

Sponsors & Collaborators

• UNICANCER: lead
• National Cancer Institute, France: collaborator
• Incyte BioSciences France: collaborator

Study Sites (6)

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, 54500, France

ACTIVE NOT RECRUITING

MeSH Terms

Interventions

pemigatinib

Study Officials

• Christophe LE TOURNEAU, Pr

  Institut Curie Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Céline MAHIER AIT OUKHATAR

CONTACT

+33 (0)6 17 51 34 29; c-mahier@unicancer.fr

Marta JIMENEZ

CONTACT

m-jimenez@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2024
• First Posted: October 22, 2024
• Study Start: March 27, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: June 5, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6)