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
Riboscience, LLC.
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.
Description
In this Phase 2a study, participants must have advanced, unresectable HCC confirmed by radiology, histology or cytology. Participants must be eligible to receive the STRIDE regimen as first line therapy. Participants must have measurable disease per RECIST 1.1, an Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1 or 2, and predicted life expectancy of at least 12 weeks. Up to approximately 220 participants will be enrolled and will receive therapy as part of their respective treatment group. Participants will receive study treatment of RBS2418 at two different dose levels (2…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. At least 18 years of age on the day of signing informed consent. 2. Male and female participants with advanced, unresectable HCC who are eligible to receive STRIDE regimen as first line therapy. 3. Willing to submit a pre-treatment tissue sample (archival or fresh tissue if archival is not available). Exclusion Criteria: 1. BCLC stage D disease at the time of screening or prior to first dose of RBS2418. 2. 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. 3. Eligible for curative treatments (…
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 (4)
- Johns HopkinsBaltimore, Maryland
- Vanderbilt-Ingram Cancer CenterNashville, Tennessee
- University of Texas SouthwesternDallas, Texas
- START Dallas Fort WorthFort Worth, Texas