Advanced Unresectable Hepatocellular CarcinomaPhase 2NCT07175441
Evaluation of RBS2418 in Combination With Tremelimumab Plus Durvalumab in Participants With Advanced Unresectable Hepatocellular Carcinoma
A Phase 2 study testing RBS2418 and STRIDE (durvalumab + tremelimumab) in people with Advanced Unresectable Hepatocellular Carcinoma, run by Riboscience, LLC. at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Unresectable Hepatocellular Carcinoma
- What is being tested?
- RBS2418 and STRIDE (durvalumab + tremelimumab)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 4 sitesUnited States
- Study dates
- 10 Apr 2026to Aug 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
Johns Hopkins
Baltimore, Maryland, 21218
- Recruiting
University of Texas Southwestern
Dallas, Texas, 75390
- Recruiting
START Dallas Fort Worth
Fort Worth, Texas, 76104
- Recruiting
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
About this study
Official title: 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
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.
Read the detailed 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 (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.
- Being tested
- RBS2418, STRIDE (durvalumab + tremelimumab)
- Keywords
- Advanced Unresectable Hepatocellular Carcinoma (HCC)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RBS2418Drug
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)Drug
STRIDE: Tremelimumab 300 mg IV (Cycle 1 Day 1 only) Plus Durvalumab 1500 mg IV every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm A: RBS2418, 200mg BID, plus STRIDE | Active comparator | RBS2418 200 mg PO, BID in combination with STRIDE regimen Receives: 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 Receives: Drug: RBS2418; Drug: STRIDE (durvalumab + tremelimumab) |
| Arm C: STRIDE alone (control) | Active comparator | STRIDE regimen Receives: Drug: STRIDE (durvalumab + tremelimumab) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Time in months from the date of randomization to the date of death from any cause.
Measured: From randomization until death from any cause, assessed up to 2 years.
Overall Response Rate (ORR) by RECIST 1.1
ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) during the study using RECIST 1.1, among those with measurable disease.
Measured: From randomization to initial response, assessed up to 2 years
Duration of Response (DOR) by RECIST 1.1
DOR is defined as time from initial response to disease progression or death.
Measured: From initial response to disease progression or death, assessed up to 2 years
Disease Control Rate (DCR)
DCR is defined as the percentage of participants who achieve a complete response (CR), partial response (PR) or stable disease (SD).
Measured: From randomization to end of treatment or disease progression, assessed up to 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2025
- Study start10 Apr 2026
- Primary completionApr 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Unresectable Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Riboscience, LLC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07175441
- Sponsor's protocol ID
- RBS2418-2002
- Status last verified
- Apr 2026
- First submitted
- 9 Sep 2025
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07175441
- Acronym / sponsor ID
- RBS2418-2002
- Keywords
- Advanced Unresectable Hepatocellular Carcinoma (HCC)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- Riboscience, LLC.Industry (pharma, biotech, devices)
- Study start
- 10 Apr 2026 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 16 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: RBS2418, 200mg BID, plus STRIDE | Active comparator | Drug: RBS2418, Drug: STRIDE (durvalumab + tremelimumab)RBS2418 200 mg PO, BID in combination with STRIDE regimen |
| Arm B: RBS2418, 800mg BID, plus STRIDE | Active comparator | Drug: RBS2418, Drug: STRIDE (durvalumab + tremelimumab)RBS2418 800 mg PO, BID in combination with STRIDE regimen |
| Arm C: STRIDE alone (control) | Active comparator | Drug: STRIDE (durvalumab + tremelimumab)STRIDE regimen |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RBS2418RBS2418 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. | Drug | Arm A: RBS2418, 200mg BID, plus STRIDE, Arm B: RBS2418, 800mg BID, plus STRIDE |
| STRIDE (durvalumab + tremelimumab)STRIDE: Tremelimumab 300 mg IV (Cycle 1 Day 1 only) Plus Durvalumab 1500 mg IV every 4 weeks | Drug | Arm A: RBS2418, 200mg BID, plus STRIDE, Arm B: RBS2418, 800mg BID, plus STRIDE, Arm C: STRIDE alone (control) |
Primary outcome
Progression Free Survival (PFS)
Time frame: From randomization until the first radiographic documentation of objective progression or death from any cause, assessed up to 2 years.
Time in months from randomization until the first radiographic documentation of objective progression, as assessed using RECIST 1.1, or death from any cause.
4 secondary outcomes
Overall Survival (OS)
Time frame: From randomization until death from any cause, assessed up to 2 years.
Overall Response Rate (ORR) by RECIST 1.1
Time frame: From randomization to initial response, assessed up to 2 years
Duration of Response (DOR) by RECIST 1.1
Time frame: From initial response to disease progression or death, assessed up to 2 years
Disease Control Rate (DCR)
Time frame: From randomization to end of treatment or disease progression, assessed up to 2 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RBS2418 and STRIDE (durvalumab + tremelimumab) in people with Advanced Unresectable Hepatocellular Carcinoma, run by Riboscience, LLC. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Riboscience Clinical Trials (415-754-3182, clinicaltrials@riboscience.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: From randomization until the first radiographic documentation of objective progression or death from any cause, assessed up to 2 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026.