A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma (FIGHT-302)

• ClinicalTrials.gov Identifier: NCT03656536
• Recruitment Status: Recruiting
• First Posted: September 4, 2018
• Last Update Posted: November 17, 2022
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: August 29, 2018
• First Posted Date: September 4, 2018
• Last Update Posted Date: November 17, 2022
• Actual Study Start Date: June 3, 2019
• Estimated Primary Completion Date: October 26, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 30, 2018)

Progression-free survival [ Time Frame: Up to approximately 12 months ]

Defined as the time from date of randomization until date of disease progression (according to Response Evaluation Criteria in Solid Tumors [RECIST] v1.1 and assessed by an independent central reviewer (ICR)) or death, whichever occurs first.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 30, 2018)

• Overall response rate [ Time Frame: Up to approximately 12 months ]
  Defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by an ICR.
• Overall survival [ Time Frame: Up to approximately 12 months ]
  Defined as the time from date of randomization until death due to any cause.
• Duration of response [ Time Frame: Up to approximately 12 months ]
  Defined as the time from the date of the first assessment of CR or PR until the date of the first disease progression by an ICR per RECIST v1.1 or death, whichever occurs first.
• Disease control rate [ Time Frame: Up to approximately 12 months ]
  Defined as the proportion of participants who achieved best overall response of CR, PR, or stable disease (SD) per RECIST v1.1 as assessed by an ICR.
• Number of treatment-emergent adverse events [ Time Frame: Up to approximately 12 months ]
  Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.
• Quality of Life impact as assessed by the EQ-5D-3L questionnaire [ Time Frame: Up to 12 months ]
• Quality of Life impact as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-30 questionnaire [ Time Frame: Up to 12 months ]
• Quality of Life impact as assessed by the EORTC QLQ-BIL21 questionnaire [ Time Frame: Up to 12 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma
• Official Title: A Phase 3, Open-Label, Randomized, Active-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Gemcitabine Plus Cisplatin Chemotherapy in First-Line Treatment of Participants With Unresectable or Metastatic Cholangiocarcinoma With FGFR2 Rearrangement (FIGHT-302)
• Brief Summary: The purpose of this study is to evaluate the efficacy and safety of pemigatinib versus gemcitabine plus cisplatin chemotherapy in first-line treatment of participants with unresectable or metastatic cholangiocarcinoma with FGFR2 rearrangement.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Unresectable Cholangiocarcinoma
• Metastatic Cholangiocarcinoma

Intervention

• Drug: Pemigatinib
  Pemigatinib at the protocol-defined dose administered orally once daily as continuous therapy schedule (a cycle is 3 weeks).
  Other Name: INCB054828
• Drug: Gemcitabine
  Gemcitabine 1000 mg/m^2 administered as an intravenous infusion on Days 1 and 8 of every 3-week cycle for up to 8 cycles.
• Drug: Cisplatin
  Cisplatin 25 mg/m^2 administered as an intravenous infusion on Days 1 and 8 of every 3-week cycle for up to 8 cycles.

Study Arms

• Experimental: Pemigatinib
  Intervention: Drug: Pemigatinib
• Active Comparator: Gemcitabine + Cisplatin
  Participants who experience disease progression while receiving gemcitabine + cisplatin or during the follow-up period and before starting a new anticancer therapy will be eligible to cross over and receive pemigatinib.
  Interventions:

  • Drug: Gemcitabine
  • Drug: Cisplatin

• Publications *: Bekaii-Saab TS, Valle JW, Van Cutsem E, Rimassa L, Furuse J, Ioka T, Melisi D, Macarulla T, Bridgewater J, Wasan H, Borad MJ, Abou-Alfa GK, Jiang P, Lihou CF, Zhen H, Asatiani E, Feliz L, Vogel A. FIGHT-302: first-line pemigatinib vs gemcitabine plus cisplatin for advanced cholangiocarcinoma with FGFR2 rearrangements. Future Oncol. 2020 Oct;16(30):2385-2399. doi: 10.2217/fon-2020-0429. Epub 2020 Jul 17.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 16, 2022): 434
• Original Estimated Enrollment (submitted: August 30, 2018): 432
• Estimated Study Completion Date: July 27, 2028
• Estimated Primary Completion Date: October 26, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male and female participants at least 18 years of age at the time of signing the informed consent form (ICF).
• Histologically or cytologically confirmed cholangiocarcinoma that is previously untreated and considered unresectable and/or metastatic (Stage IV per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual).
• Radiographically measurable or evaluable disease by CT or MRI per RECIST v1.1 criteria.
• Eastern Cooperative Oncology Group performance status 0 to 1.
• Documented FGFR2 rearrangement.
• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• Received prior anticancer systemic therapy for unresectable and/or metastatic disease (not including adjuvant/neo-adjuvant treatment completed at least 6 months prior to enrollment, and participants that have received treatment for locally advanced disease with trans-arterial chemoembolization or selective internal radiation therapy, if clear evidence of radiological progression is observed before enrollment, or enrolled as of Amendment 6 (or Amendment 5-JP2) and the participant received 1 cycle of gemcitabine plus cisplatin [the start of study drug {Cycle 1 Day 1} must be at least 14 days and ≤ 4 weeks {28 days} from the last dose of gemcitabine plus cisplatin]).
• Child-Pugh B and C.
• Toxicities related to prior therapy(ies) must be Common Terminology Criteria for Adverse Events (CTCAE) v5.0 ≤ Grade 1 at the time of screening.
• Concurrent anticancer therapy, other than the therapies being tested in this study.
• Participant is a candidate for potentially curative surgery.
• 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 central serous retinopathy, macular/retinal degeneration, diabetic retinopathy, retinal detachment) as confirmed by ophthalmologic examination.
• Radiation therapy administered within 4 weeks of enrollment/randomization/first dose of study treatment.
• Known central nervous system (CNS) metastases or history of uncontrolled seizures.
• Known additional malignancy that is progressing or requires active treatment (exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
• Laboratory values at screening outside the protocol-defined range.
• 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 the skin, kidney, tendons or vessels due to injury, disease, and aging, in the absence of systemic mineral imbalance).
• Significant gastrointestinal disorders that could interfere with absorption, metabolism, or excretion of pemigatinib.
• Clinically significant or uncontrolled cardiac disease.
• History or presence of an abnormal ECG, which, in the investigator's opinion, is clinically meaningful.
• Chronic or current active infectious disease requiring systemic antibiotics or antifungal or antiviral treatment within 2 weeks prior to enrollment (participants with asymptomatic chronic infections on prophylactic treatment are allowed). Note: HIV-positive participants are allowed if all of the following criteria are met: CD4+ count ≥ 300/µL, undetectable viral load, receiving antiretroviral therapy that does not interact with study drug, and no HIV/AIDS-associated opportunistic infection in the last 12 months.
• 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 treatment. Note: Moderate CYP3A4 inhibitors are not prohibited
• Known hypersensitivity or severe reaction to pemigatinib, gemcitabine, cisplatin, or their excipients.
• Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Incyte Corporation Call Center (US); 1.855.463.3463; medinfo@incyte.com

Contact: Incyte Corporation Call Center (ex-US); +800 00027423; globalmedinfo@incyte.com

• Listed Location Countries: Austria, Belgium, Canada, China, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Japan, Netherlands, Norway, Spain, Sweden, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT03656536
• Other Study ID Numbers: INCB 54828-302
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• URL: https://www.incyte.com/our-company/compliance-and-transparency

• Current Responsible Party: Incyte Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Incyte Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Peter Langmuir, MD; Incyte Corporation

• PRS Account: Incyte Corporation
• Verification Date: November 2022