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

NCT06027086 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: J23107IRB00388561
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Fibrolamellar Hepatocellular Carcinoma

Keywords

Fibrolamellar Carcinoma (FLC); Durvalumab; DRP-104 (glutamine antagonist); Immunotherapy; Anti PD-L1; PD-L1; Carcinoma; Glutamine antagonist

Outcome Measures

Primary Outcomes (2)

• Number of participants experiencing drug-related adverse events (AEs) requiring treatment discontinuation

  When calculating the incidence of AEs, each AE (as defined by NCI Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0) will be counted only once for a given subject.

  4 years

• Objective response rate (ORR) using immune Response Evaluation Criteria for Solid Tumors (RECIST 1.1)

  ORR is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) to DRP-104 (glutamine antagonist) in combination with duvalumab, based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30percent decrease in sum of diameters of target lesions, progressive disease (PD) is \>20percent increase in sum of diameters of target lesions, stable disease (SD) is \<30percent decrease or \<20percent increase in sum of diameters of target lesions.

  4 years

Secondary Outcomes (2)

• Progression-free Survival (PFS)

  4 years

• Overall survival (OS)

  4 years

Study Arms (1)

Durvalumab and DRP-104

EXPERIMENTAL

Drug: Durvalumab; Drug: DRP-104

Interventions

Durvalumab DRUG

Patients will receive treatment on Day 1 of each cycle. Durvalumab (1500 mg) will be administered IV on Day 1 of each cycle every 28 days.

Also known as: IMFINZI

Durvalumab and DRP-104

DRP-104 DRUG

Patients will receive treatment twice a week of each cycle. DRP-104 (145 mg,125mg, 105mg, 85mg or 65mg) will be administered subcutaneous injection twice a week of each 28 day cycle. After the first cycle of treatment the study drug may be shipped to the patient's home for future cycles of administration if patients or caregiver can demonstrate at least two observed independent injections of DRP-104 prior to home administration.

Durvalumab and DRP-104

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Dracen Pharmaceuticals, Inc.: collaborator
• Fibrolamellar Cancer Foundation: collaborator

Study Sites (1)

Johns Hopkins SKCCC

Baltimore, Maryland, 21231, United States

RECRUITING

MeSH Terms

Conditions

Fibrolamellar hepatocellular carcinoma; Carcinoma

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Marina Baretti, MD

  SKCCC • Johns Hopkins Medical Institution

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Colleen Apostal, RN

CONTACT

410-614-3644; GIClinicalTrials@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2023
• First Posted: September 7, 2023
• Study Start: February 12, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2033
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)