A Phase II Study of Pemigatinib Plus Durvalumab in Previously Treated Advanced Intrahepatic Cholangiocarcinoma Patients With FGFR-2 Fusion or Rearrangement

NCT06728410 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN-GI23-621
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

FGFR2 Gene Rearrangement; Intrahepatic Cholangiocarcinoma; FGFR2 Gene Mutation

Outcome Measures

Primary Outcomes (1)

• 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.

  24 months

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  24 months

• Disease Control Rate (DCR)

  24 months

• Overall Survival

  24 months

• Duration of response

  24 months

• Number of Participants with Adverse Events

  24 months

Study Arms (1)

Pemigatinib + Durvalumab

EXPERIMENTAL

Pemigatinib 13.5 mg will be taken orally at the same time each day for 14 days (Day 1 through Day 14), followed by 7 days off treatment (Day 15 through Day 21) of each 21 day cycle. Durvalumab 1500 mg IV will be administered every 3 weeks on Day 1 of each 21-day cycle.

Drug: Pemigatinib; Drug: Durvalumab

Interventions

Pemigatinib DRUG

Pemigatinib 13.5 mg

Also known as: PEMAZYRE

Pemigatinib + Durvalumab

Durvalumab DRUG

Durvalumab 1500 mg IV

Also known as: Imfinzi

Pemigatinib + Durvalumab

Eligibility Criteria

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

You may qualify if:

• 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.
• Histologically diagnosed locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma with FGFR-2 fusion or rearrangement detected by Clinical Laboratory Improvement Act (CLIA)-certified assays including commercial tests (Foundation Medicine, Caris, Tempus, Guardant 360 or other platforms of next generation sequencing will be allowed). AJCC, 8th edition. Subjects with gallbladder cancer or ampulla of Vater carcinoma are not eligible.
• Measurable disease according to RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have received gemcitabine cisplatin and durvalumab or another anti-PD-1 Ab for unresectable locally advanced or metastatic cholangiocarcinoma with either disease progression, intolerance to cytotoxic chemotherapy, or have received at least 6 months of therapy with stable disease or partial response. Prior neoadjuvant or adjuvant therapy is permitted if documented disease recurrence occurred ≥ 6 months after the last date of neoadjuvant or adjuvant therapy.
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.
• Absolute Neutrophil Count (ANC): ≥1500/µL
• Hemoglobin (Hgb): ≥ 9 g/dL; Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
• Platelet (PLT): ≥ 100 000/µL
• Calculated creatinine clearance: \>40 mL/min
• Bilirubin: ≤ 1.5 × upper limit of normal (ULN) This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with the sponsor-investigator.
• Aspartate aminotransferase (AST): ≤ 2.5 × institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
• Alanine aminotransferase (ALT): ≤ 2.5 × institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN

You may not qualify if:

• 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.
• History of hypovitaminosis D requiring supraphysiologic doses (eg, 50,000 UI/weekly) to replenish the deficiency. Vitamin D supplements are allowed.
• Participation in another clinical study with an investigational product during the last 3 months
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤ 28 days prior to the first dose of study regimen. If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by sponsor-investigator.
• Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the sponsor-investigator.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with the study regimen may be included only after consultation with the sponsor-investigator.
• Any concurrent chemotherapy, study drug, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study regimen.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study regimen. NOTE: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:

Sponsors & Collaborators

• Mehmet Akce: lead
• AstraZeneca: collaborator
• Incyte Corporation: collaborator
• University of Alabama at Birmingham: collaborator

Study Sites (2)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

pemigatinib; durvalumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Mehmet Akce, MD

  Sponsor-Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mehmet Akce, MD

CONTACT

205-801-9034; makce@uabmc.edu

Ahran Lee

CONTACT

317-634-5842; alee@hoosiercancer.org

Study Design

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

Study Record Dates

• First Submitted: December 6, 2024
• First Posted: December 11, 2024
• Study Start: January 27, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)