Evaluation of RBS2418 in Subjects With Advanced, Metastatic Solid Tumors
ConditionAdvanced Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorRiboscience, LLC.
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Be willing and able to provide written informed consent for the study. The subject may also provide consent for Future biomedical research (FBR). However, the subject may participate in the main study without participating in FBR.
18 years of age on day of signing informed consent.
Male and female subjects with advanced unresectable, recurrent or metastatic tumors who have received standard of care (SOC) therapy for their advanced/metastatic tumors and have no other SOC therapy available. Additionally, subjects must have received, have been intolerant to, have been ineligible for, or have declined all SOC therapies known to confer significant clinical benefit.
Have histologically or cytologically confirmed cancer diagnosis based on pathology report.
Disqualifiers
Palliative radiotherapy for bone metastases or soft tissue lesions should be completed > 7 days prior to baseline imaging
Hormone-replacement therapy or oral contraceptives
Subjects with Grade 2 neuropathy or Grade 2 alopecia
Subjects with evidence of rapid progression on prior therapy resulting in rapid clinical deterioration should be excluded from participation in the trial.
Trial design
Design model
Single group
Treatments tested in this trial
RBS2418
DrugRBS2418 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.
Pembrolizumab
Drug200 mg intravenously every 3 weeks
Other approved anti-cancer therapy
DrugStandard of care (SOC) therapy
Treatment groups
164 Participants
are divided into 3 treatment groupsGroup A: Treatment Group A-1 (Completed)Experimental treatment 1 intervention
Group B: Treatment Group A-2 (Completed)Experimental treatment 2 interventions
Group C: Treatment Group BExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Treatment emergent dose limiting toxicities (DLT)
When more than 1 DLT occurs in ≤ 6 patients in a dosing cohort, MTD has been exceeded and no more patients are to be treated at that dose level. No DLT observed at the highest dose level in Part A. Part A has been completed.
Time frame
From 1- 21 days of the first cycle (each cycle is 21 days)2
Peak plasma concentration (Cmax) of RBS2418
maximum plasma concentration of RBS2418
Time frame
Day 0 - 53
Area under the plasma concentration versus time curve (AUC)
area under the curve for RBS2418
Time frame
Day 0 - 54
Optimal Biologically Active Dose (OBA)
Dose at which Ctrough plasma concentration of RBS2418 equal to or higher than ENPP1 EC90 in human serum is achieved. All dose levels (100-800 mg BID) achieved the endpoint. Part A has been completed.
Time frame
Day 0 - 5Secondary outcomes
1
Overall response rate (ORR) by RECIST
Beginning with screening, all imaging assessments will be evaluated using RECIST 1.1. On- study imaging assessments will be performed Q9W. RECIST 1.1 will be used by the site for treatment decisions until the first radiographic evidence of PD.
Time frame
nine weeks from first doseSponsors and contacts
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Source ClinicalTrials.gov