Clinical trial evaluating the efficacy of pemigatinib for the treatment of patients with solid tumours with an alteration of the gene FGFR

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Mar 2025 → ongoing

Decision date (initial)

2024-10-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Inca

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate the efficacy of pemigatinib monotherapy on tumor growth kinetics and tumoral response in patients with recurrent and/or metastatic cancer harboring a FGFR alteration (fusion/rearrangement or activating mutation).

Secondary objectives 9

1. Efficacy_Overall response rate (ORR)
2. Efficay_Clinical benefit rate (CBR)
3. Efficacy_Duration of response (DoR)
4. Efficacy_Progression-free survival
5. Efficacy_Time to treatment failure
6. Effucacy_Overall survival
7. To assess the safety and tolerability of pemigatinib
8. To evaluate the quality of life
9. Exploratory objective_To study the relevance of efficacy monitoring using longitudinal ctDNA sampling

Conditions and MedDRA coding

Recurrent or metastatic solid cancer harboring a FGFR1,2 ,3 fusion/rearrangement or activating mutation, outside of the approved indications for any selective FGFR inhibitor in France

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Histologically or cytologically confirmed solid tumor
2. Patient with locally reccurent unresectable and/or advanced or metastatic disease harbouring a FGFR1,2,3 fusion/rearrangement or mutation (appendix 8 of the protocol)
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 may derive a benefit, according to the physician assessment,
6. Estimated life expectancy >3 months
7. Mesurable disease according to RECIST1.1, whatever the disease location. Tumor lesions located in a previously irradiated area, or in an area subjected to other locoregional 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: 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: ALT and AST < 2,5 x ULN (≤ 5 x ULN for liver metastasis); total bilirubin < 1.5 x ULN (< 2.5 x ULN if Gilbert’s syndrome or liver metastasis); ALP < 3 x ULN
12. Adequate renal function: serum creatinine clearance > 30 mL/minute based on Cockroft-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 (WOCBP) 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 23

1. Hematologic malignancies
2. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. A screening QTcF interval > 480 ms is excluded.
3. 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
4. Known hypersensitivity or severe reaction to pemigatinib or excipients of pemigatinib (refer to the Investigator Brochure)
5. 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)
6. Patient who received prior selective FGFR inhibitor
7. Patient who can be included in a recruiting study assessing FGFR inhibitor (including pemigatinib)
8. 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-CNS 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)
9. 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
10. 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
11. 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
12. Current evidence of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination
13. 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
14. 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)
15. Significant gastrointestinal disorder(s) that could interfere with absorption, metabolism, or excretion of pemigatinib
16. Known HIV infection except if undetectable viral load
17. 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)
18. Inability to swallow and retain oral medication
19. 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)
20. Women who are pregnant or breastfeeding
21. History of hypovitaminosis D requiring supraphysiologic doses (eg, 50,000 UI/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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients experiencing an objective response or at least a 30% decrease in tumor growth kinetics at PD on study treatment as compared to one calculated from the two pre-treatment tumor evaluations. Tumor kinetics variation is measured by tumor growth ratio (TGr) defined as the ratio of the slope of tumor growth on treatment (between the nadir and PD) and slope of tumor growth before treatment. Sum of diameters of target lesions calculated on each patient's imaging by BICR

Secondary endpoints 9

1. ORR defined as the proportion of patients with a complete response (CR) or a partial response (PR) as best overall response during the study, based on RECIST1.1, as assessed by the BICR and by the physician.
2. CBR defined as the proportion of patients with a complete response (CR) or a partial response (PR) or a stable disease (SD) lasting ≥ 24 weeks (6 months) as best overall response during the study, based on RECIST1.1, as assessed by the BICR and by the physician.
3. Duration of response (DoR) measured in responder patients from the time of first documented response (CR or PR) until the first documented disease progression (according to RECIST1.1) or death due to any cause, as assessed by the BICR and by the physician.
4. PFS measured from the date of inclusion to the date of event defined as the first documented disease progression (according to RECIST1.1) or death from any cause, whichever occurs first as assessed by the BICR and by physicians. Patients with no event at the time of analysis will be censored at the date of last adequate tumor assessment.
5. TTF defined as the time from the date of inclusion to the date of permanent study treatment discontinuation (any cause, including disease progression, treatment toxicity and death, withdrawal of consent). Patients without treatment failure at the time of the analysis will be censored at the date of last tumor assessment
6. OS measured from the date of inclusion to the date of death from any cause. Patients who are alive at the time of analysis (including lost to follow-up) will be censored at the date of last contact.
7. Safety and tolerability, as assessed by the occurrence of TEAEs and treatmentrelated AEs according to NCI CTCAE v5.0
8. QoL (pre, 3- and 6-months post-treatment initiation, and EOT) EORTC QLQ-C30.
9. EXPLORATORY ENDPOINTS: Longitudinal assessment of FGFR alterations on ctDNA.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris Cedex 13

Postcode

75654

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications