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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
14
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Progression-free Survival (PFS)
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).
Time frame: 6 months
Overall Response Rate (ORR)
ORR defined as the number of evaluable patients achieving a response \[partial response or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1\] during treatment. Complete Response (CR): All of the following must be true: a. Disappearance of all target lesions. b. Each target lymph node must have reduction in short axis to \<1.0 cm. c. Normalization of tumor biomarkers. Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD (baseline sum of dimensions).
Time frame: 3 years
Overall Survival (OS)
OS is defined as the time from registration to death due to any cause. Median OS time and 95% CI will be reported.
Time frame: 4 years
Incidence of Adverse Events
Adverse events will be evaluated per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for each patient. Number of participants experiencing one or more grade 3+ adverse events will be reported.
Time frame: 4 years
Change in Quality of Life (QOL)
As measured by the global health domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30), version 3. Change in score between baseline and first re-staging will be calculated for each individual. Twenty-eight (28) questions are answered on a scale of 1-4 where 1=not at all, 2=a little, 3=quite a bit, and 4= very much. The final two questions are answered on a scale of 1-7 where 1= very poor and 7=excellent. Raw scores were then scored according to EORTC guidelines (Fayers PM, Aaronson NK, Bjordal K, Groenvold M, Curran D, Bottomley A on behalf of the EORTC Quality of Life Group. EORTC QLQ-C30 Scoring Manual (3rd edition). Brussels: EORTC, 2001.), so that scores are 0-100, with a higher score indicating a better quality of life.
Time frame: 3 years
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