RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

Official Title

A Phase 1b/2 Study of Glutamine Antagonist DRP-104 in Combination With Durvalumab in Patients With Advanced Stage Fibrolamellar Hepatocellular Carcinoma (FLC)

Quick Facts

Study Start:2024-02-12

Study Completion:2029-08-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06027086

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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

Inclusion Criteria

Exclusion 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.

* 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

Contacts and Locations

Study Contact

Colleen Apostal, RN

CONTACT

410-614-3644

GIClinicalTrials@jhmi.edu

Joann Santmyer, RN

CONTACT

410-614-3644

GIClinicalTrials@jhmi.edu

Principal Investigator

Marina Baretti, MD

PRINCIPAL_INVESTIGATOR

SKCCC • Johns Hopkins Medical Institution

Study Locations (Sites)

Johns Hopkins SKCCC

Baltimore, Maryland, 21231

United States

Collaborators and Investigators

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Marina Baretti, MD, PRINCIPAL_INVESTIGATOR, SKCCC • Johns Hopkins Medical Institution

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-02-12

Study Completion Date2029-08-01

Study Record Updates

Study Start Date2024-02-12

Study Completion Date2029-08-01

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Fibrolamellar Hepatocellular Carcinoma