drp-104 (glutamine antagonist) in combination with durvalumab in patients with advanced stage fibrolamellar carcinoma (flc)

Conditions: Fibrolamellar Hepatocellular Carcinoma

Summary: 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).


Eligibility criteria:
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 \<92% on room air or is on supplemental home oxygen. * active or untreated brain metastases or leptomeningeal metastases. * uncontrolled intercurrent active medical and/or psychiatric illness/social psychosocial problems that that would limit compliance with study requirements. * uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements. * pregnant or breastfeeding. * has a known history of human immunodeficiency virus (hiv)/aids. * has active hepatitis b. patients with chronic or acute hepatitis b virus (hbv) infection . * have had evidence of active or acute diverticulitis, intra-abdominal abscess, or gi obstruction which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study. * patient is unwilling or unable to follow the study schedule for any reason. * patient is at the time of signing informed consent a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol). * evidence of clinical ascites. * participants a with history of prior unacceptable and/or life-threatening toxicities attributed to anti-programmed death-receptor 1 (pd1) or anti-pd-l1 (anti-programmed death-receptor 1) therapy. * has active autoimmune disease that has required systemic treatment in the past 2 years. * prior allogeneic stem cell transplantation or organ transplantation. * has a diagnosis of immunodeficiency. * systemic corticosteroids at immunosuppressive doses. * patients who have had either of the following procedures or medications within 4 weeks prior to initiation of study treatment: * any live, attenuated vaccine * allergen hypo sensitization therapy in the last 2 weeks

Keywords: fibrolamellar carcinoma (flc) durvalumab drp-104 (glutamine antagonist) immunotherapy anti pd-l1 pd-l1 carcinoma glutamine antagonist