Combining DRP-104 and Durvalumab for treating advanced Fibrolamellar Carcinoma

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

This study is testing if a new combination of two treatments, DRP-104 and Durvalumab, can help people with advanced Fibrolamellar Carcinoma feel better and live longer after their previous treatments didn't work.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Academic / other)
• Drugs / interventions: durvalumab, chemotherapy, immunotherapy, radiation
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT06027086 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and effectiveness of the combination of DRP-104, a glutamine antagonist, and Durvalumab, an anti-PD-L1 immunotherapy, in patients with advanced stage Fibrolamellar Carcinoma (FLC). The primary goal is to assess the antitumor activity through objective response rates, while secondary objectives include evaluating progression-free survival and overall survival. Eligible participants must have confirmed metastatic or unresectable FLC and have shown progression on prior immunotherapy. The study will also involve collecting tissue and blood samples for further research.

Who should consider this trial

Good fit: Ideal candidates are patients aged 12 and older with histologically confirmed metastatic or unresectable Fibrolamellar Carcinoma who have experienced disease progression on prior immunotherapy.

Not a fit: Patients with early-stage Fibrolamellar Carcinoma or those who have not received prior immunotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new therapeutic option for patients with advanced Fibrolamellar Carcinoma.

How similar studies have performed: Other studies have shown promise in using immunotherapy for treating various cancers, but this specific combination is novel and has not been extensively tested.

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

Where this trial is running

Baltimore, Maryland

• Johns Hopkins SKCCC — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Marina Baretti, MD — SKCCC • Johns Hopkins Medical Institution
• Study coordinator: Colleen Apostal, RN

Conditions Fibrolamellar Hepatocellular Carcinoma; Fibrolamellar Carcinoma; Durvalumab; DRP-104; Immunotherapy; Anti PD-L1; PD-L1; Carcinoma