Carolina BioOncology Institute | Huntersville, NC
Status and phase
Conditions
Treatments
About
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 checkpoint blockade. This study is an open-label, multi-site Phase 1a/1b study of RBS2418, a selective ENPP1 inhibitor, in combination with pembrolizumab or as a monotherapy in subjects with advanced unresectable, recurrent or metastatic tumors.
Full description
In this Phase 1a/b study, 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).
Approximately 24 - 64 subjects will be enrolled and will receive therapy as part of their respective treatment groups (ascending doses of RBS2418 of 100 mg, 200 mg, 400 mg and 800 mg BID as monotherapy or in combination with pembrolizumab 200 mg IV q3w). The study consists of two (2) phases. The first part of the study (Part A) is the dose escalation phase of the study and is planned to enroll up to 8 cohorts in total (3-6 subjects per cohort) to receive RBS2418 as monotherapy or in combination with pembrolizumab to identify the fixed dose to be evaluated further in the expansion phase of the study (Part B) (~20-40 subjects).
A "3+3" design will be used to establish dose limiting toxicities (DLT), the maximum tolerated dose and the dose level of RBS2418 corresponding to an optimal biologically active dose to aid in the selection of the fixed expansion cohort dose.
In all treatment arms, treatment will continue 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 in combination with pembrolizumab, 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
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Exclusion criteria
Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 1; or if subject has not recovered (i.e., Less than or equal to Grade 1 or returned to baseline level) from adverse events due to a previously administered agent; the following exceptions are allowed:
Subjects with evidence of rapid progression on prior therapy resulting in rapid clinical deterioration should be excluded from participation in the trial.
Currently participating and receiving trial therapy or has participated in a trial of an investigational agent and/or has used an investigational device within 28 days prior to Day 1.
Uncontrolled tumor-related pain
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
Malignancies other than indications open for enrollment within 3 years prior to Day 1, with the exception of those with negligible risk of metastasis or death treated with expected curative outcome, undergoing active surveillance or treatment-naïve for indolent tumors
Treatment with systemic immunomodulating agents (including but not limited to Interferons (IFNs), Interleukin-2 (IL-2), anti-PD-1/PD-L1 inhibitors, ipilimumab) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to first dose.
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
Known hypersensitivity allergy or contraindication to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the PD-1/PD-L1 inhibitor formulation.
Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
History or any evidence of interstitial lung disease
Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment.
Active HIV requiring therapy and Uncontrolled HIV*. HIV antibody testing recommended per investigator's clinical suspicion.
Severe infections within 4 weeks prior to enrollment, including, but not limited to, hospitalization for complications of infection, bacteremia, or the presence of any active infection requiring systemic therapy.
Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 1
Received a live, attenuated vaccine within 28 days prior to enrollment/cohort assignment or anticipation that such a live attenuated vaccine will be required during the trial
Primary purpose
Allocation
Interventional model
Masking
64 participants in 3 patient groups
Loading...
Central trial contact
Riboscience Clinical Trials
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal