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

NCT ID: NCT06027086

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-12
• Study Completion Date: 2033-09-01

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Durvalumab and DRP-104

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: 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.

DRP-104

Intervention Type: 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.

Interventions

Durvalumab

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.

Intervention Type: DRUG

DRP-104

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.

Intervention Type: DRUG

Other Intervention Names

IMFINZI

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dracen Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Fibrolamellar Cancer Foundation

OTHER

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marina Baretti, MD

Role: PRINCIPAL_INVESTIGATOR

SKCCC • Johns Hopkins Medical Institution

Locations

Johns Hopkins SKCCC

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Colleen Apostal, RN

Role: CONTACT

GIClinicalTrials@jhmi.edu

410-614-3644

Facility Contacts

Colleen Apostal, RN

Role: primary

GIClinicalTrials@jhmi.edu

410-614-3644

Other Identifiers

IRB00388561

Identifier Type: OTHER

Identifier Source: secondary_id

J23107

Identifier Type: -

Identifier Source: org_study_id