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

Trial Summary

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.

What data supports the effectiveness of the drug DRP-104 + Durvalumab for cancer?

Durvalumab, a part of the treatment, has shown effectiveness in treating various cancers, including non-small-cell lung cancer and urothelial carcinoma, by enhancing the body's immune response against cancer cells. It has been approved for use in certain cancers and is being tested in combination with other treatments, showing promising results. ^{1 2 3 4 5}

Is the combination of DRP-104 and Durvalumab safe for humans?

Durvalumab, also known as Imfinzi, has been studied in various cancers and generally shows a manageable safety profile, though it can cause side effects like reduced appetite and diarrhea. In combination with other drugs, it has shown a higher rate of serious side effects, but these are still considered manageable. ^{1 2 3 4 6}

What makes the drug DRP-104 + Durvalumab unique for cancer treatment?

The combination of DRP-104 and Durvalumab is unique because it pairs a novel drug with an established immune checkpoint inhibitor, Durvalumab, which blocks PD-L1 to enhance the body's immune response against cancer cells. This combination aims to improve efficacy by targeting cancer cells more effectively than using Durvalumab alone. ^{1 2 3 4 7}

What is the purpose of this trial?

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).

Research Team

Marina Baretti, MD

Principal Investigator

SKCCC • Johns Hopkins Medical Institution

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

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, 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

2. United States 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. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

5. United States 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. [2022]

6. Switzerland 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. [2019]