DRP-104 + Durvalumab for Cancer

Overseen By Joann Santmyer, RN

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: CYP 3A4/5 inducers, Corticosteroids

Disqualifiers: Brain metastases, HIV/AIDS, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 years

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of cancer treatments: DRP-104 (also known as Sirpiglenastat, an experimental treatment) and Durvalumab (an immunotherapy drug), to determine their safety and effectiveness in shrinking tumors. It targets individuals with Fibrolamellar Carcinoma (FLC), a rare liver cancer that has spread or cannot be surgically removed. The trial seeks participants whose cancer has progressed despite previous treatments. Suitable candidates have FLC with a specific genetic marker and have experienced cancer growth despite other immunotherapy treatments. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as chemotherapy, biological cancer therapy, or radiation, at least 21 days before starting the study drug. Additionally, if you are taking potent inducers of Cytochrome P450 3A (CYP 3A4/5), you must discontinue them at least 14 days before the trial begins.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Durvalumab, also known as Imfinzi, has been tested in many types of cancer and is generally safe. It can cause side effects, but they are usually manageable. Studies indicate that even when combined with another treatment, it remains safe for most people.

Early research on DRP-104 focuses on understanding its safety for humans. These studies are in the initial stages, so researchers are still learning about its safety. Since this trial is in the early phases, safety is closely monitored.

In summary, Durvalumab is considered safe for many cancer patients, while DRP-104 is still under study to determine its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about DRP-104 combined with Durvalumab because this treatment approach targets cancer cells in a novel way. Unlike standard treatments that might focus solely on stopping cell growth, DRP-104 works by altering the tumor's metabolism, effectively starving the cancer cells. When paired with Durvalumab, an immunotherapy that boosts the body's immune response against cancer, this combination could potentially enhance the effectiveness against tumors more than existing options. This dual-action method could offer new hope for patients by attacking cancer from two different angles, which is why it's generating interest in the medical community.

What evidence suggests that the combination of DRP-104 and Durvalumab could be effective for cancer?

In this trial, participants will receive a combination of DRP-104 and Durvalumab. Research has shown that this combination holds promise in fighting cancer. DRP-104 blocks glutamine, which helps stop cancer growth, and its effects strengthen when used with Durvalumab. Durvalumab boosts the immune system to attack cancer cells. Studies have indicated that this combination allows patients to live for an average of 3.6 months without their cancer worsening. It has also shown safety and may improve outcomes for cancer patients. Overall, early evidence suggests this treatment could be effective against certain types of cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Marina Baretti, MD

Principal Investigator

SKCCC • Johns Hopkins Medical Institution

Are You a Good Fit for This Trial?

This trial is for individuals aged 12 or older with advanced Fibrolamellar Carcinoma (FLC) that can't be removed by surgery. They must have confirmed FLC with specific genetic features, shown progression on immunotherapy, and meet certain health criteria including organ function. Participants need to provide tissue samples and use birth control.

Inclusion Criteria

I am using or willing to use birth control during the study.

Must have measurable disease per RECIST 1.1

My kidney and liver are working well according to recent tests.

Exclusion Criteria

Patients with corrected QT interval (QTc) prolongation > 470 ms according to Fridericia formula.

You are currently using illegal drugs or have recently had a problem with drugs or alcohol.

I am unable to follow the study's schedule.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous DRP-104 in combination with intravenous Durvalumab

4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• DRP-104
• Durvalumab

Trial Overview The study tests the safety and effectiveness of DRP-104 combined with Durvalumab in treating FLC. It measures tumor response rates, how long patients live without disease progression, and overall survival time after treatment.

How Is the Trial Designed?

Group I: Durvalumab and DRP-104 Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Fibrolamellar Cancer Foundation

Collaborator

Trials

4

Recruited

110+

Fibrolamellar Cancer Foundation

Collaborator

Trials

3

Recruited

80+

Dracen Pharmaceuticals, Inc.

Industry Sponsor

Trials

2

Recruited

90+

Published Research Related to This Trial

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

The combination of MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

The combination of durvalumab and tremelimumab showed improved disease control rates in patients with head and neck squamous cell carcinoma compared to tremelimumab alone, indicating its potential efficacy in this cancer type.

The combination therapy had a tolerable safety profile, with no significant increase in treatment-related adverse events compared to monotherapy, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis. Wang, BC., Li, PC., Fan, JQ., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06027086

Study Details | NCT06027086 | DRP-104 (Glutamine ... 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 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.TPS573

Glutamine antagonist DRP-104 in combination with ... We are conducting a single-arm phase 1b/2 clinical trial of glutamine antagonist DRP-104 in combination with durvalumab in children (age ≥ 12) and adults with ...

3. fibrofoundation.org fibrofoundation.org/press-releases/the-fibrolamellar-cancer-foundation-and-dracen-pharmaceuticals-announce-launch-of-clinical-trial/

The Fibrolamellar Cancer Foundation and Dracen ... Phase I/II study of DRP-104 in combination with Durvalumab to be tested in patients with fibrolamellar carcinoma (FLC) ... FCF and Dracen recently ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35930753/

Sirpiglenastat (DRP-104) Induces Antitumor Efficacy ... Finally, DRP-104 demonstrated significant antitumor activity as a monotherapy, which was further enhanced in combination with checkpoint ...

5. withpower.com withpower.com/trial/phase-2-carcinoma-2024-ed8f9

DRP-104 + Durvalumab for Cancer Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02087423?term=AREA%5BBasicSearch%5D(AREA%5BInterventionSearch%5D(DURVALUMAB%20OR%20MEDI4736%20OR%20MEDI-4736%20OR%20Imfinzi))&rank=10

A Global Study to Assess the Effects of MEDI4736 ... This study is designed to investigate the efficacy, safety, tolerability of a new drug, MEDI4736 (Durvalumab), in patients with Locally Advanced or ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04471415

NCT04471415 | Study to Investigate DRP-104 in Adults ... The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmaco-dynamics and preliminary anti-tumor activity of DRP-104 ...

8. dana-farber.org dana-farber.org/clinical-trials/22-260

Phase 1 and phase 2a, first-in-human study of DRP-104, a ... The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmaco-dynamics and preliminary anti-tumor activity of DRP-104.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...