RBS2418 + Tremelimumab + Durvalumab for Liver Cancer

Overseen By Riboscience Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Riboscience, LLC.

Must be taking: CTLA-4 inhibitors

Disqualifiers: BCLC stage D, Child-Pugh B8, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments to determine if they work better together against liver cancer. It focuses on a new drug, RBS2418, designed to boost the body's immune response to cancer, alongside Tremelimumab and Durvalumab, both immunotherapy drugs. The goal is to see if this combination can improve outcomes for individuals with advanced liver cancer that cannot be surgically removed. Suitable candidates for this trial have inoperable liver cancer and can begin treatment with the STRIDE regimen. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that RBS2418 was well-tolerated in early studies. Tests with 19 patients revealed that different doses did not cause any serious side effects. The treatment was deemed safe, as no severe problems occurred at any dose tested.

Tremelimumab and Durvalumab are established treatments in cancer therapy. They have been used together in the STRIDE regimen for liver cancer. Since these drugs are approved for other conditions, their safety is well-documented, although individual reactions can vary.

Overall, combining RBS2418 with Tremelimumab and Durvalumab aims to be both safe and effective. However, as with any treatment, it is important to consider all potential risks and benefits and discuss them with healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for liver cancer because they combine innovative therapies that may enhance immune system responses. Durvalumab and Tremelimumab are both immune checkpoint inhibitors, which work by blocking proteins that prevent the immune system from attacking cancer cells. RBS2418 is unique because it's an investigational agent designed to potentially boost the effectiveness of these immune therapies through a novel mechanism. This combination could offer a more robust attack on liver cancer cells compared to current standard treatments like sorafenib or lenvatinib, which primarily target cancer growth pathways. By harnessing and strengthening the body’s own immune response, these treatments hold the promise of improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for liver cancer?

Research has shown that RBS2418 might help fight liver cancer by boosting the immune system. It stops an enzyme called ENPP1 from breaking down a molecule known as cGAMP, which activates immune cells to attack cancer. In animal studies, RBS2418 significantly slowed tumor growth and extended survival. In this trial, some participants will receive RBS2418 combined with the STRIDE treatment, which includes Tremelimumab and Durvalumab. This combination is expected to enhance the body's ability to fight tumors and might be more effective than the STRIDE treatment alone, which is being tested in a separate arm of the trial. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

Adults with advanced, unresectable hepatocellular carcinoma (a type of liver cancer) can join this trial. Participants should not have had prior treatments for their cancer and must be able to handle the side effects of immunotherapy.

Inclusion Criteria

Willing to submit a pre-treatment tissue sample (archival or fresh tissue if archival is not available)

I am at least 18 years old.

I have advanced liver cancer and can receive STRIDE as my first treatment.

Exclusion Criteria

My liver cancer is at an advanced stage (BCLC stage D).

My liver function is classified as moderately impaired.

I am a candidate for treatments aimed at curing my condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RBS2418 at two different dose levels in combination with STRIDE or STRIDE alone in 28-day cycles up to two years or until progression, death, withdrawal, or study completion

Up to 2 years

Follow-up

Participants are monitored for adverse events and overall survival after treatment

Up to 90 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• RBS2418
• Tremelimumab

Trial Overview The study is testing RBS2418 combined with a known immunotherapy regimen called STRIDE (Tremelimumab plus Durvalumab). It's designed to see if adding RBS2418 improves the body's immune response against liver cancer compared to using STRIDE alone.

How Is the Trial Designed?

Group I: Arm C: STRIDE alone (control) Active Control 1 Intervention

STRIDE regimen

Group II: Arm B: RBS2418, 800mg BID, plus STRIDE Active Control 2 Interventions

RBS2418 800 mg PO, BID in combination with STRIDE regimen

Group III: Arm A: RBS2418, 200mg BID, plus STRIDE Active Control 2 Interventions

RBS2418 200 mg PO, BID in combination with STRIDE regimen

Who Is Running the Clinical Trial?

Riboscience, LLC.

Lead Sponsor

Trials

3

Recruited

210+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07175441

Study Details | NCT07175441 | Evaluation of RBS2418 in ... The hypothesis is that RBS2418 combined with STRIDE will be safe, well-tolerated, highly immunogenic, and enhance anti-tumor responses in adult ...

2. patlynk.com patlynk.com/trial/NCT07175441

RBS2418, Tremelimumab, and Durvalumab for Advanced ... This study focuses on testing a combination of medications for people with advanced liver cancer, specifically those whose cancer cannot be surgically removed. ...

3. mountsinai.org mountsinai.org/clinical-trials/rbs2418-evaluation-in-subjects-with-unresectable-metastatic-tumors

Evaluation of RBS2418 in Subjects With Advanced ... Have histologically or cytologically confirmed cancer diagnosis based on pathology report. 5. Have a predicted life expectancy of greater or equal to 3 months.

4. vanderbilt.trialstoday.org vanderbilt.trialstoday.org/trial/NCT05270213

Evaluation of RBS2418 in Subjects With Advanced, ... RBS2418 has the potential to be an important therapeutic option for subjects both as monotherapy and in combination with other cancer treatments ...

5. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/2472/741183/Abstract-2472-Inhibition-of-ENPP1-catalyzed-ATP

Abstract 2472: Inhibition of ENPP1 catalyzed ATP and cGAMP ... In the Hepa1-6 model treatment with RBS2418 for either 2 or 10 days resulted in significant reduction of tumor growth and prolongation of ...

6. reporter.nih.gov reporter.nih.gov/project-details/11183063

Project Details - NIH RePORTER Riboscience has successfully advanced an ENPP1 inhibitor, RBS2418, to Phase 1a/1b and the clinical results have demonstrated that RBS2418 can fully inhibit ...

7. withpower.com withpower.com/trial/phase-2-advanced-unresectable-hepatocellular-carcinoma-9-2025-5e51a

RBS2418 + Tremelimumab + Durvalumab for Liver Cancer The hypothesis is that RBS2418 combined with STRIDE will be safe, well-tolerated, highly immunogenic, and enhance anti-tumor responses in adult participants ...

8. esmoiotech.org esmoiotech.org/article/S2590-0188(22)00212-X/pdf

169P Immunomodulatory effects of RBS2418, an oral ... Liver mets were shown to negatively predict the success of immuno- therapy (as opposed to chemotherapy [chemo] or targeted therapy) in several cancer types.

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03001-6/pdf

Methods Results: The first 3 dose levels evaluated to date in 19 patients were safe and well tolerated with no DLTs. Median plasma concentrations of RBS2418 increased ...