RecruitingPhase 2NCT07175441

Evaluation of RBS2418 in Combination With Tremelimumab Plus Durvalumab in Participants With Advanced Unresectable Hepatocellular Carcinoma

A Phase 2a, Multicenter, Randomized, Open-Label Study to Assess the Efficacy, Safety, and Tolerability of RBS2418 in Combination With Tremelimumab Plus Durvalumab for Participants With Advanced Unresectable Hepatocellular Carcinoma


Sponsor

Riboscience, LLC.

Enrollment

220 participants

Start Date

Apr 1, 2026

Study Type

INTERVENTIONAL

Conditions

Summary

RBS2418 is a targeted immune modulator that inhibits ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). It is designed to promote anti-tumor immunity by preserving endogenous 2'-3' cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from hydrolysis, thereby activating antigen-presenting cells and promoting robust T cell activation. Ideally, RBS2418 acts synergistically with CTLA-4 inhibitors, such as those in the STRIDE regimen (Tremelimumab plus Durvalumab). The hypothesis is that RBS2418 combined with STRIDE will be safe, well-tolerated, highly immunogenic, and enhance anti-tumor responses in adult participants with advanced, unresectable hepatocellular carcinoma (HCC) compared to STRIDE alone.


Eligibility

Min Age: 18 Years

Inclusion Criteria3

  • At least 18 years of age on the day of signing informed consent.
  • Male and female participants with advanced, unresectable HCC who are eligible to receive STRIDE regimen as first line therapy.
  • Willing to submit a pre-treatment tissue sample (archival or fresh tissue if archival is not available).

Exclusion Criteria4

  • BCLC stage D disease at the time of screening or prior to first dose of RBS2418.
  • Child-Pugh class equal or higher than B8 at the time of screening or within 7 days prior to the first dose of study treatment.
  • Eligible for curative treatments (e.g., surgical resection, liver transplantation, or local ablation).
  • Evidence of rapid progression on prior therapy resulting in rapid clinical deterioration.

Interventions

DRUGRBS2418

RBS2418 is a specific immune modulator that works through the inhibition of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and is designed to lead to anti-tumor immunity by protecting endogenous 2'-3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from hydrolysis and leading to the activation of antigen-presenting cells followed by T cell activation.

DRUGSTRIDE (durvalumab + tremelimumab)

STRIDE: Tremelimumab 300 mg IV (Cycle 1 Day 1 only) Plus Durvalumab 1500 mg IV every 4 weeks


Locations(3)

Johns Hopkins

Baltimore, Maryland, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

START Dallas Fort Worth

Fort Worth, Texas, United States

View Full Details on ClinicalTrials.gov

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NCT07175441