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
Overview
- Phase
- Phase 2
- Intervention
- Futibatinib
- Conditions
- Advanced Hepatocellular Carcinoma
- Sponsor
- Mayo Clinic
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- Progression-free Survival (PFS)
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
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.
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.
Investigators
Eligibility Criteria
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)
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
Arms & Interventions
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.
Intervention: Futibatinib
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.
Intervention: Pembrolizumab
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.
Intervention: Quality-of-Life Assessment
Outcomes
Primary Outcomes
Progression-free Survival (PFS)
Time Frame: 6 months
PFS is defined as the length of time from study registration until disease progression. For the purposes of this study, 6 months is defined as 27 weeks. Percent of patients alive and progression free will be reported, estimated using the method of Kaplan-Meier. Progression will be evaluated in this study using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1).
Secondary Outcomes
- Overall Response Rate (ORR)(3 years)
- Overall Survival (OS)(4 years)
- Incidence of Adverse Events(4 years)
- Change in Quality of Life (QOL)(3 years)