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

Riboscience

Status and phase: Enrolling; Phase 2

Conditions: Advanced Unresectable Hepatocellular Carcinoma

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT07175441

RBS2418-2002

Details and patient eligibility

About

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.

Full 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.

Enrollment: 220 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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220 participants in 3 patient groups

Arm A: RBS2418, 200mg BID, plus STRIDE

Active Comparator group

Description:

RBS2418 200 mg PO, BID in combination with STRIDE regimen

Treatment:

Drug: RBS2418

Drug: STRIDE (durvalumab + tremelimumab)

Arm B: RBS2418, 800mg BID, plus STRIDE

Active Comparator group

Description:

RBS2418 800 mg PO, BID in combination with STRIDE regimen

Treatment:

Drug: RBS2418

Drug: STRIDE (durvalumab + tremelimumab)

Arm C: STRIDE alone (control)

Active Comparator group

Description:

STRIDE regimen

Treatment:

Drug: STRIDE (durvalumab + tremelimumab)