NCT05270213

Evaluation of RBS2418 in Subjects With Advanced, Metastatic Solid Tumors

A First-In-Human, Phase 1 a/b Dose Escalation and Expansion Study to Evaluate RBS2418 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Unresectable, Recurrent or Metastatic Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 164 (estimated)
• Sponsor: Riboscience, LLC. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RBS2418 (investigational product) is a specific immune modulator, working through ectonucleotide pyrophosphatase/phosphodiesterase I (ENPP1), designed to lead to anti-tumor immunity by increasing endogenous 2'-3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) and adenosine triphosphate (ATP levels) and reducing adenosine production in the tumors. RBS2418 has the potential to be an important therapeutic option for subjects both as monotherapy and in combination with other cancer treatments including monotherapy and in combination with other cancer treatments including immunotherapy or chemotherapy. This study is an open-label, multi-site Phase 1a/1b study of RBS2418, a selective ENPP1 inhibitor, in combination with pembrolizumab or other approved anticancer therapies or as a monotherapy in subjects with advanced unresectable, recurrent or metastatic tumors. The phase 1a (dose escalation phase) has been completed. The Phase 1b expansion phase of the study has been increased in size and scope.

Detailed description

The dose escalation phase (Part A) of this Phase 1a/1b study has been completed (n=24 study participants). Based on safety and preliminary activity data, we have expanded the size and scope of the dose expansion phase (Part B), which will include treatment groups receiving RBS2418 at selected dose levels. These doses will be administered either as monotherapy or in combination with approved anti-cancer therapies, including pembrolizumab (200 mg IV every 3 weeks), or other standard-of-care therapies at the discretion of the site principal investigator (PI). Part B is enrolling approximately 140 subjects to further assess safety, tolerability, and preliminary efficacy at selected doses in expansion cohorts. Subjects must have received standard of care (SOC) therapy for their advanced/metastatic tumors and subjects must have received, have been intolerant to, have been ineligible for, or have declined all treatment known to confer significant clinical benefit. Subjects must also have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST1.1), an Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1 or 2 and predicted life expectancy of greater than 3 months. An imaging scan is required at baseline, up to 28 days prior to treatment initiation. Subjects are required to provide an adequate tumor tissue sample (archival or fresh-tissue if no archival is available). In all treatment arms, treatment continues until progressive disease (PD), unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdrawal of consent, pregnancy of the subject, noncompliance with study dosing or procedure requirements, subject receiving approximately 2 years of RBS2418 monotherapy or combination therapy, or administrative reasons requiring cessation of treatment. After the last dose of study drug, each subject will be followed for 30 days for AE monitoring. Serious adverse events (SAEs) will be collected for 90 days after the end of treatment or for 30 days after the end of treatment, if the subject initiates new anticancer therapy, whichever is earlier

Conditions

• Advanced Cancer

Interventions

Type	Name	Description
DRUG	RBS2418	RBS2418 is a potent and selective small molecule inhibitor of ectonucleotide pyrophosphatase/phosphodiesterase I (ENPP1). RBS2418 as monotherapy potentially can have an activating effect on the anti-tumor innate immune response and lead to anti-tumor responses in adult subjects with advanced or metastatic tumors.
DRUG	Pembrolizumab	200 mg intravenously every 3 weeks
DRUG	Other approved anti-cancer therapy	Standard of care (SOC) therapy

Timeline

• Start date: 2022-07-11
• Primary completion: 2027-04-01
• Completion: 2027-12-01
• First posted: 2022-03-08
• Last updated: 2025-12-19

Locations

14 sites across 1 country: United States

Regulatory

• FDA-regulated drug study