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

NCT ID: NCT07175441

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-31

Study Completion Date

2027-08-31

Brief Summary

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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.

Detailed Description

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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 (200mg and 800mg) twice daily in combination with STRIDE or STRIDE alone with a treatment period consisting of 28-day cycles up to two years or until there is progressive disease, death, withdrawal, or study completion, whichever comes first.

Adverse Events (AEs) will be monitored throughout the study and graded in severity according to the guidelines outlined in the NCI CTCAE v5.0. AEs will be collected until up to 30 days after the last dose of RBS2418 or until resolution, whichever comes first. SAEs will be collected for 90 days after the last dose of RBS2418, or if the participant initiates new anti-cancer therapy, then 30 days after the RBS2418 last dose, whichever is earlier.

Conditions

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Advanced Unresectable Hepatocellular Carcinoma

Keywords

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Advanced Unresectable Hepatocellular Carcinoma (HCC)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: RBS2418, 200mg BID, plus STRIDE

RBS2418 200 mg PO, BID in combination with STRIDE regimen

Group Type ACTIVE_COMPARATOR

RBS2418

Intervention Type 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.

STRIDE (durvalumab + tremelimumab)

Intervention Type DRUG

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

Arm B: RBS2418, 800mg BID, plus STRIDE

RBS2418 800 mg PO, BID in combination with STRIDE regimen

Group Type ACTIVE_COMPARATOR

RBS2418

Intervention Type 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.

STRIDE (durvalumab + tremelimumab)

Intervention Type DRUG

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

Arm C: STRIDE alone (control)

STRIDE regimen

Group Type ACTIVE_COMPARATOR

STRIDE (durvalumab + tremelimumab)

Intervention Type DRUG

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

Interventions

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RBS2418

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.

Intervention Type DRUG

STRIDE (durvalumab + tremelimumab)

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Riboscience, LLC.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Johns Hopkins

Baltimore, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Riboscience Clinical Trials

Role: CONTACT

Phone: 415-754-3182

Email: [email protected]

Other Identifiers

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RBS2418-2002

Identifier Type: -

Identifier Source: org_study_id