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

NCT07175441 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: RBS2418-2002
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Advanced Unresectable Hepatocellular Carcinoma

Keywords

Advanced Unresectable Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Time in months from randomization until the first radiographic documentation of objective progression, as assessed using RECIST 1.1, or death from any cause.

  From randomization until the first radiographic documentation of objective progression or death from any cause, assessed up to 2 years.

Secondary Outcomes (4)

• Overall Survival (OS)

  From randomization until death from any cause, assessed up to 2 years.

• Overall Response Rate (ORR) by RECIST 1.1

  From randomization to initial response, assessed up to 2 years

• Duration of Response (DOR) by RECIST 1.1

  From initial response to disease progression or death, assessed up to 2 years

• Disease Control Rate (DCR)

  From randomization to end of treatment or disease progression, assessed up to 2 years.

Study Arms (3)

Arm A: RBS2418, 200mg BID, plus STRIDE

ACTIVE COMPARATOR

RBS2418 200 mg PO, BID in combination with STRIDE regimen

Drug: RBS2418; Drug: STRIDE (durvalumab + tremelimumab)

Arm B: RBS2418, 800mg BID, plus STRIDE

ACTIVE COMPARATOR

RBS2418 800 mg PO, BID in combination with STRIDE regimen

Drug: RBS2418; Drug: STRIDE (durvalumab + tremelimumab)

Arm C: STRIDE alone (control)

ACTIVE COMPARATOR

STRIDE regimen

Drug: STRIDE (durvalumab + tremelimumab)

Interventions

RBS2418 DRUG

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.

Arm A: RBS2418, 200mg BID, plus STRIDE; Arm B: RBS2418, 800mg BID, plus STRIDE

STRIDE (durvalumab + tremelimumab) DRUG

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

Arm A: RBS2418, 200mg BID, plus STRIDE; Arm B: RBS2418, 800mg BID, plus STRIDE; Arm C: STRIDE alone (control)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Riboscience, LLC.: lead

Study Sites (4)

Johns Hopkins

Baltimore, Maryland, 21218, United States

RECRUITING

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

University of Texas Southwestern

Dallas, Texas, 75390, United States

RECRUITING

START Dallas Fort Worth

Fort Worth, Texas, 76104, United States

RECRUITING

MeSH Terms

Interventions

durvalumab; tremelimumab

Central Study Contacts

Riboscience Clinical Trials

CONTACT

415-754-3182; clinicaltrials@riboscience.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2025
• First Posted: September 16, 2025
• Study Start: April 10, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)