Futibatinib and Pembrolizumab for Treatment of Advanced or Metastatic FGF19 Positive BCLC Stage A, B, or C Liver Cancer

January 16, 2024 updated by: Mayo Clinic

Phase II Study of FGFR Inhibitor Futibatinib in Combination With Anti-PD-1 Antibody Pembrolizumab in Patients With Advanced or Metastatic Hepatocellular Carcinoma With FGF19 Expression After First Line Therapy

This phase II trial studies the effect of futibatinib and pembrolizumab in treating patients with FGF19 positive BCLC stage A, B, or C liver cancer that has spread to other parts of the body (advanced or metastatic). Futibatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving futibatinib and pembrolizumab may help treat patients with FGF19 positive liver cancer.

Study Overview

Detailed Description

PRIMARY OBJECTIVE:

I. Determine the efficacy of combination of futibatinib and pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) and high FGF19 expression who has received at least one line of therapy using progression free survival (PFS) at 6 months.

SECONDARY OBJECTIVES:

I. Assess the safety and tolerability of futibatinib and pembrolizumab combination through adverse event monitoring.

II. Determine the overall objective response rate (ORR) and overall survival (OS) of patients with advanced HCC treated with futibatinib and pembrolizumab combination.

III. Assess change in overall health-related quality of life, as measured by the global health domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) between baseline and at time of first-restaging scan.

EXPLORATORY OBJECTIVES:

I. To evaluate the prognostic effect of baseline number of circulating tumor cells (CTCs).

II. To determine whether the change in number of CTCs post 2 months of treatment from baseline is associated with PFS and OS.

III. To evaluate the prognostic effect of baseline circulating cell-free deoxyribonucleic acid (cfDNA).

IV. To determine whether the change in cfDNA at 2 months of treatment from baseline is associated with PFS and OS.

V. To correlate drug response in patient derived organoids with clinical response and characterize the tumor microenvironment.

OUTLINE:

Patients receive futibatinib orally (PO) once daily (QD) on days 1-21 for cycles 1-9, and days 1-42 for subsequent cycles and pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for cycles 1-9 and every 42 days for subsequent cycles for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completing study treatment, patients are followed up at 30 days, every 9 weeks for up to 18 months, and then every 6 months for up to 5 years.

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Principal Investigator:
          • Nguyen H. Tran, M.D.
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age >= 18 years
  • Adequate tissue for FGF19 testing by ribonucleic acid (mRNA) or immunohistochemistry (IHC)
  • Disease characteristics:

    • Radiologically or pathologically confirmed hepatocellular carcinoma (HCC) that is not eligible for curative resection, transplantation, or ablative therapies
    • NOTE: Prior radiation, chemoembolization, radioembolization, or other local ablative therapies or hepatic resection are permitted
  • Measurable disease by any imaging modality as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in at least one site not previously treated with radiation or liver directed therapy (including bland, chemo- or radio-embolization, or ablation)

    • NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease; disease that is measurable by physical examination only is not eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (=< 15 days prior to registration)
  • Hemoglobin >= 8.0 g/dL (=< 15 days prior to registration)
  • Platelet count >= 75,000/mm^3 (=< 15 days prior to registration)
  • Albumin >= 2.5 g/dL (=< 15 days prior to registration)
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 2.5 x upper limit of normal (ULN) (or =< 5 x ULN for patients with liver metastasis) (=< 15 days prior to registration)
  • Total bilirubin =< 2 x ULN (=< 15 days prior to registration)
  • Phosphorus =< 1.5 x ULN (=< 15 days prior to registration)
  • Calcium =< 1.5 x ULN (=< 15 days prior to registration)
  • Prothrombin time/international normalized ratio/activated partial thromboplastin time (PT/INR/aPTT) =< 1.5 x ULN OR if patient is receiving anticoagulant therapy then INR or aPTT is within target range of therapy (=< 15 days prior to registration)
  • Calculated creatinine clearance >= 40 ml/min using the Cockcroft-Gault formula (=< 15 days prior to registration)
  • Child-Pugh scores of =< 7 (Child-Pugh A or B7)
  • Barcelona Clinic Liver Cancer Stage (BCLC) stage A, B, or C
  • Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
  • Willing to use an adequate method of contraception from registration through 120 days after the last dose of study medication

    • NOTE: Only for a) persons of childbearing potential or b) persons able to father a child with partners of childbearing potential
  • Able to swallow oral medication
  • Provide written informed consent
  • Willingness to provide mandatory blood specimens for correlative research
  • Willingness to provide mandatory tissue specimens for correlative research
  • Willingness and the ability to comply with scheduled visits (including geographical proximity), treatment plans, laboratory tests, and other study procedures
  • Ability to complete questionnaires by themselves or with assistance

Exclusion Criteria:

  • Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
  • Eligible for first-line treatment with IMbrave150 or STRIDE regimens
  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

    • Pregnant persons
    • Nursing persons
    • Persons of childbearing potential who are unwilling to employ adequate contraception
  • Any of the following prior therapies:

    • Surgery =< 4 weeks prior to registration
    • Radiotherapy for extended field =< 4 weeks prior to registration or limited field radiotherapy =< 2 weeks prior to registration
    • Systemic anticancer therapy =< 2 weeks prior to registration

      • NOTE: Prior immunotherapy is allowed unless patient discontinued due to grade 4 adverse event (AE)
    • Live vaccine =< 30 days prior to registration
    • Prior treatment with FGFR inhibitor
    • Received strong inhibitors and inducers and sensitive substrates of CYP3A4 =< 2 weeks prior to registration
    • Received a drug that has not received regulatory approval for any indication as follows:

      • =< 2 weeks prior to registration for nonmyelosuppressive agents or
      • =< 4 weeks prior to registration for myelosuppressive agents
  • History and/or current evidence of any of the following disorders:

    • Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant in the opinion of the Investigator
    • Pneumonitis or interstitial lung disease within =< 3 years prior to registration
  • Active central nervous system (CNS) metastasis and/or carcinomatous meningitis

    • NOTE: Patients with previously treated brain metastases that are clinically and radiologically stable (for at least 4 weeks prior to enrollment) are eligible
  • Corrected QT interval using Fridericia's formula (QTcF) > 480 msec

    • NOTE: Patients with an atrioventricular pacemaker or other condition (for example, right bundle branch block) that renders the QT measurement invalid are an exception and the criterion does not apply
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis. Notes:

    • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
    • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible.
    • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:

      • Must not have ocular manifestations
      • Rash must cover less than 10% of body surface area (BSA)
      • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
      • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  • Known active human immunodeficiency virus (HIV) infection (defined as patients who are not on anti-retroviral treatment and have detectable viral load and CD4+ < 500/ml)

    • NOTE: HIV-positive patients who are well controlled on anti-retroviral therapy are allowed to enroll
  • History and/or current evidence of any of the following disorders:

    • Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator
    • Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator
    • Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant in the opinion of the Investigator
  • Uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active severe infection

      • NOTE: Must be afebrile > 7 days to be eligible. Patient may be eligible if fever is present and infection has been ruled out or fever is related to tumor
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from day 1 of study treatment administration, New York Heart Association class III and IV congestive heart failure, and uncontrolled arrhythmia

    • NOTE: Participants with pacemaker or with atrial fibrillation and well controlled heart rate are allowed
  • Other active malignancy <6 months prior to pre-registration

    • EXCEPTIONS: Non-melanotic skin cancer, papillary thyroid cancer, or carcinoma-in-situ of the cervix, or others curatively treated and now considered to be at less than 30% risk of relapse are eligible
  • Prior organ transplantation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (futibatinib, pembrolizumab)
Patients receive futibatinib PO QD on days 1-21 for cycles 1-9, and days 1-42 for subsequent cycles and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for cycles 1-9 and every 42 days for subsequent cycles for up to 2 years in the absence of disease progression or unacceptable toxicity.
Ancillary studies
Other Names:
  • Quality of Life Assessment
Given IV
Other Names:
  • Keytruda
  • MK-3475
  • Lambrolizumab
  • SCH 900475
Given PO
Other Names:
  • TAS-120
  • Lytgobi

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: At 6 months
PFS will be calculated using the Kaplan-Meier method.
At 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: Up to 5 years
ORR defined as the number of evaluable patients achieving a response (partial response or complete response per Response Evaluation Criteria in Solid Tumors v1.1) during treatment with study therapy divided by the total number of evaluable patients. Point estimates will be generated for objective response rates along with 95% binomial confidence intervals.
Up to 5 years
Overall survival (OS)
Time Frame: Time from registration to death due to any cause, assessed up to 5 years
The distribution of survival time will be estimated using the method of Kaplan-Meier. OS medians will be estimated along with 95% confidence intervals.
Time from registration to death due to any cause, assessed up to 5 years
Incidence of adverse events
Time Frame: Up to 5 years
Adverse events will be evaluated, per Common Terminology Criteria for Adverse Events version 5.0, for each patient.
Up to 5 years
Change in quality of life (QOL)
Time Frame: Up to 5 years
As measured by the global health domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The median QOL change from baseline along with a 95% confidence interval will be estimated using the Hodges-Lehmann method.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Nguyen H. Tran, M.D., Mayo Clinic in Rochester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 7, 2021

Primary Completion (Estimated)

September 6, 2024

Study Completion (Estimated)

May 6, 2025

Study Registration Dates

First Submitted

March 30, 2021

First Submitted That Met QC Criteria

March 30, 2021

First Posted (Actual)

April 2, 2021

Study Record Updates

Last Update Posted (Actual)

January 18, 2024

Last Update Submitted That Met QC Criteria

January 16, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • MC200402 (Mayo Clinic in Rochester)
  • NCI-2021-02444 (Registry Identifier: CTRP (Clinical Trials Reporting Program))
  • 20-007235 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Advanced Hepatocellular Carcinoma

Clinical Trials on Quality-of-Life Assessment

3
Subscribe