This is a single arm phase II study of pemigatinib and durvalumab combination in patients with FGFR-2 fusion or rearrangement positive intrahepatic cholangiocarcinoma. Each cycle will be 3 weeks. Pemigatinib is administered at 13.5 mg orally daily 2 weeks on and 1 week off. Durvalumab is administered at 1500 mg intravenously once every 3 weeks. Subjects will require a visit with appropriate laboratory work prior to the start of each cycle. Disease assessment will occur every 9 weeks. Subjects will continue treatment until progression per RECIST 1.1, toxicity or subject/physician decision. A maximum of 24 months (about 35 cycles) of pemigatinib and durvalumab treatment from Cycle 1 Day 1 is allowed.
Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18 years at the time of consent.
ECOG Performance Status of 0 or 1.
Body weight of > 30 kg.
Prior therapy with a FGFR inhibitor.
Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to macular/retinal degeneration, diabetic retinopathy, and retinal detachment) as confirmed by ophthalmologic examination
History of calcium and phosphate homeostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues such as the skin, kidney tendon, or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance)
Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug. Moderate CYP3A4 inhibitors are not prohibited but should be avoided.
Single group
Pemigatinib
DrugPemigatinib 13.5 mg
Durvalumab
DrugDurvalumab 1500 mg IV
Confirmed objective response rate (ORR)
ORR will include confirmed complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST version 1.1. A confirmed response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart.
Progression Free Survival (PFS)
PFS is defined as the time from Day 1 of treatment until the criteria for disease progression is met as defined by RECIST version 1.1 or death as a result of any cause.
Disease Control Rate (DCR)
DCR (per RECIST 1.1 as assessed by the Investigator) is defined as the rate of best objective response of CR, PR, or SD according to RECIST 1.1. DCR is defined as the percentage of subjects who have a best objective response of CR or PR or who have SD for at least 9 weeks (±7 days) following the start of study treatment.
Overall Survival
OS is defined as the time from Day 1 of treatment until death from any cause.
Duration of response
DOR (per RECIST 1.1 as assessed by the Investigator) will be defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response). The end of response should coincide with the date of progression or death from any cause used for the RECIST 1.1 PFS endpoint.
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Mehmet Akce
Lead sponsor
Hoosier Cancer Research Network
Sponsor institution
AstraZeneca
Collaborator
Incyte Corporation
Collaborator
University of Alabama at Birmingham
Collaborator
