RBS2418 with tremelimumab and durvalumab for advanced unresectable liver cancer

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

This trial will test whether adding RBS2418 to tremelimumab plus durvalumab helps adults with advanced, unresectable hepatocellular carcinoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Riboscience, LLC. (Industry-sponsored)
• Drugs / interventions: Tremelimumab, Durvalumab
• Locations: 4 sites (Baltimore, Maryland and 3 other locations)
• Trial ID: NCT07175441 on ClinicalTrials.gov

What this trial studies

This Phase 2a, randomized study enrolls up to ~220 adults with radiologically or pathologically confirmed advanced, unresectable HCC who are eligible for the STRIDE regimen as first-line therapy. Participants receive either STRIDE alone or STRIDE plus RBS2418 at one of two dose levels (200 mg or 800 mg twice daily) in 28-day cycles for up to two years or until progression or withdrawal. The trial measures safety (AEs per NCI CTCAE v5.0), immunogenicity, and anti-tumor activity by RECIST 1.1, with regular imaging and laboratory monitoring. Pre-treatment tissue is required and participants must have ECOG 0-2 and a predicted life expectancy of at least 12 weeks.

Who should consider this trial

Good fit: Adults (≥18) with advanced, unresectable HCC who are eligible for STRIDE as first-line therapy, have measurable disease per RECIST 1.1, ECOG performance status 0–2, a predicted life expectancy ≥12 weeks, and can provide a pre-treatment tissue sample are ideal candidates.

Not a fit: Patients with BCLC stage D disease, Child-Pugh class ≥B8, those eligible for curative treatments (resection, transplant, local ablation), or those with rapid clinical deterioration on prior therapy are excluded and unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding RBS2418 could strengthen anti-tumor immune responses and improve tumor control compared with STRIDE alone.

How similar studies have performed: The STRIDE regimen (tremelimumab plus durvalumab) has shown clinical benefit in HCC in prior trials such as HIMALAYA, but clinical data for ENPP1 inhibitors like RBS2418 are limited so this specific combination remains largely experimental.

Eligibility criteria

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 (e.g., surgical resection, liver transplantation, or local ablation).
4. Evidence of rapid progression on prior therapy resulting in rapid clinical deterioration.

Where this trial is running

Baltimore, Maryland and 3 other locations

• Johns Hopkins — Baltimore, Maryland, United States (Recruiting)
• Vanderbilt-Ingram Cancer Center — Nashville, Tennessee, United States (Recruiting)
• University of Texas Southwestern — Dallas, Texas, United States (Recruiting)
• START Dallas Fort Worth — Fort Worth, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Riboscience Clinical Trials

Conditions Advanced Unresectable Hepatocellular Carcinoma