DRP-104 (Glutamine Antagonist) in Combination With Durvalumab in Patients With Advanced Stage Fibrolamellar Carcinoma (FLC)

The purpose of this study is to determine whether the combination of subcutaneous DRP-104 in combination with intravenous Durvalumab is safe and yields a clinically compelling antitumor activity measured as based on objective response rate (ORR, assessed by RECIST 1.1). Secondary objectives include progression-free survival (PFS) and overall survival (OS).

Inclusion Criteria: * Must have histologically confirmed FLC (Fibrolamellar Carcinoma) that is metastatic or unresectable. * Presence of DNAJB1-PRKACA fusion transcript, assessed by RNA-sequencing, DNA-sequencing, or in situ hybridization in the archival tissue. * Must have demonstrated radiographic progression on prior or current immunotherapy. * Age ≥ 12 years. * Patients \< 18 years old must have a body weight ≥ 40 kg. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 * Patients must have adequate organ and marrow function defined by study-specified laboratory tests. * Patients must have adequate kidney and liver function defined by study-specified laboratory tests. * Must have measurable disease per RECIST 1.1 * Willingness to provide tissue and blood samples for mandatory translational research. * Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test. * For both Women and Men, must use acceptable form of birth control while on study. * Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: * Must have had chemotherapy or other systemic therapy or radiotherapy, as follows: * Patients who have had chemotherapy, biological cancer therapy, or radiation 21 days prior to the first dose of study drug. * Patients who have had surgery within 28 days of dosing of investigational agent, excluding minor procedures. * Patients who have received other approved or investigational agents or device within 21 days of the first dose of study drug. * Patients who have not recovered from acute adverse events to grade ≤1 or baseline due to agents administered, with exception of grade 2 fatigue, rash, and endocrinopathy successfully managed hormone replacement therapy, or alopecia or stable neuropathy, unless approved by the investigational new drug (IND) Sponsor. * Patients with corrected QT interval (QTc) prolongation \> 470 ms according to Fridericia formula. * Patients receiving potent inducers of Cytochrome P450 3A (CYP 3A4/5) (including apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin and St. John's Wort) that cannot be discontinued at least 14 days prior to Cycle 1 Day 1. * Known sensitivity to or history of allergic reactions attributed to compounds of similar chemical or biologic composition of DRP-104 or durvalumab. * Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity. * Has a pulse oximetry of \