Exploiting a Critical Vulnerability to Glutamine Antimetabolite Therapy in Fibrolamellar Hepatocellular Carcinoma (FLC)

Timeframe: 2023 – 2028 Goals: Assess the potential of an inhibitor of glutamine metabolism (DRP-104; sirpiglenastat) in combination with an immune checkpoint inhibitor (durvalumab) as a treatment option for unresectable disease Principal Investigators: Marina Baretti, MD and Mark Yarchoan, MD Study overview: This phase Ib/2 clinical study, led by Dr. Marina Baretti and Dr. Mark …

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Multicenter consortium to define the single-cell activity landscape of fibrolamellar carcinoma.

Timeframe: 2022 – 2024 Goals: Advance immunotherapy for FLC by defining promising immunological targets that can be translated into effective cell-based immunotherapies Principal Investigators: Praveen Sethupathy, PhD (Cornell University); Mark Yarchoan, MD (Johns Hopkins University); Paul G. Thomas, PhD (St. Jude Children’s Research Hospital) Study overview: Like tumors of other cancer types, the microenvironment of …

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Clinical trial protocol development

Timeframe: 2022 – 2023 Goals: Accelerate development of potential clinical trial Principal Investigator: Mark Yarchoan, MD Study overview: This grant to Dr. Yarchoan is meant to support the development of a protocol for a potential clinical trial. In 2020, the Johns Hopkins team began a phase I clinical trial of an experimental vaccine containing a …

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A Pilot Study of a DNAJB1-PRKACA fusion kinase vaccine combined with nivolumab and ipilimumab for patients with fibrolamellar carcinoma (FLC)

Timeframe: 2019 – 2023 Goal: Assess potential to induce immune response with a FLC therapeutic vaccine Principal Investigator: Mark Yarchoan, MD Study overview: Many patients with FLC currently receive an immune checkpoint inhibitor off-label. These drugs “take the brakes off” the immune system, enhancing its ability to fight cancer. However, clinical experience suggests that they …

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Generation of T cells with specificity to FLC’s chimeric fusion

Timeframe: 2016 – 2017 Goals: Determine if T cells can be generated that react to FLC’s characteristic fusion protein Principal Investigator: Ephraim Fuchs, MD Study overview: In FLC, the characteristic DNAJB1-PRKACA fusion creates a novel protein with a unique amino acid sequence occurring at the junction of these two proteins.  This unique amino acid sequence …

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Sequential related donor partial liver followed by bone marrow transplantation for treatment of extensive, liver-confined fibrolamellar hepatocellular carcinoma (FL-HCC)

Timeframe: 2014 – 2018 Goals: Develop and implement a clinical trial for combined liver and bone marrow transplantation as a treatment for liver-confined FLC Principal Investigator: Ephraim Fuchs, MD Study overview: This grant supported the development of a phase II, single center study to assess the feasibility and effectiveness of combining bone marrow transplantation and …

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Investigating immune checkpoint biomarkers in tissue and peripheral blood of patients with fibrolamellar hepatocellular carcinoma

Timeframe: 2016 – 2019 Goal: Define the dominant immune checkpoint pathway in FLC Principal investigator: Amy K. Kim, MD Study overview: Tumor cells produce immune checkpoint molecules that suppress host immune response and allow evasion from immune responses. The discovery of drugs that block these immune checkpoints have revolutionized current cancer treatment. Anti-PD1 (programmed cell …

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Blood markers for fibrolamellar

Timeframe: 2010 Goal: Identify biomarkers for FLC Principal Investigator: Michael Torbenson, MD (Currently at Mayo Clinic) Study overview: Early identification of tumors is essential for aggressive treatment. The majority of fibrolamellar carcinoma (FLC) patients have metastatic disease at the time of diagnosis. Therefore, identification of biomarkers for FLC is essential. Using a broad collection of …

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