Evaluation of RBS2418 in Subjects With Advanced, Metastatic Solid Tumors

NCT05270213 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: RBS2418-1001
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 14

Brief 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.

Conditions

Advanced Cancer

Keywords

Metastatic tumors; Recurrent tumors; Unresectable tumors

Outcome Measures

Primary Outcomes (6)

• 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.

  From 1- 21 days of the first cycle (each cycle is 21 days)

• Peak plasma concentration (Cmax) of RBS2418

  maximum plasma concentration of RBS2418

  Day 0 - 5

• Area under the plasma concentration versus time curve (AUC)

  area under the curve for RBS2418

  Day 0 - 5

• 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.

  Day 0 - 5

• Half-life (t1/2)

  half-life of RBS2418

  Day 0 - 5

• Number of participants with treatment emergent Adverse events

  Adverse events, as graded by NCI CTCAE v5.0 including adverse events of special interest (AESI) classified by system organ class, preferred term, severity and relationship to drug

  30 days from last dose

Secondary Outcomes (1)

• Overall response rate (ORR) by RECIST

  nine weeks from first dose

Study Arms (3)

Treatment Group A-1 (Completed)

EXPERIMENTAL

For Treatment Group A-1, a cohort of three (3) subjects will be dosed at the starting dose of 100 mg twice a day (BID) of RBS2418. Subsequent subjects will then be enrolled in serial, three (3) subject cohorts, with 100% dose increments (doubling the dose) until 800 mg BID

Drug: RBS2418

Treatment Group A-2 (Completed)

EXPERIMENTAL

For Treatment Group A-2, a cohort of three (3) subjects will be dosed at the starting dose of 100 mg twice a day (BID) of RBS2418 in combination with pembrolizumab 200 mg IV (administered on Day 1 and every 3 weeks). Subsequent subjects will then be enrolled in serial, three (3) subject cohorts, with 100% dose increments (doubling the dose) until 800 mg BID

Drug: RBS2418; Drug: Pembrolizumab

Treatment Group B

EXPERIMENTAL

RBS2418 as Monotherapy or in combination with investigator-selected approved anticancer therapy at selected dose levels. (n\~140)

Drug: RBS2418; Drug: Pembrolizumab; Drug: Other approved anti-cancer therapy

Interventions

RBS2418 DRUG

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.

Treatment Group A-1 (Completed); Treatment Group A-2 (Completed); Treatment Group B

Pembrolizumab DRUG

200 mg intravenously every 3 weeks

Treatment Group A-2 (Completed); Treatment Group B

Other approved anti-cancer therapy DRUG

Standard of care (SOC) therapy

Treatment Group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Have a predicted life expectancy of greater or equal to 3 months.
• Have measurable disease based on RECIST 1.1.
• Have a performance status of 0, 1 or 2 using the ECOG Performance Scale within 14 days of first dose of study drug.
• Willing to submit a pre-treatment (archival or fresh-tissue if no archival tissue is available) and on-treatment tissue sample. Subjects in whom the treating physician deems such biopsy is clinically contraindicated will be evaluated on a case-by-case basis for enrollment pending Sponsor consultation.
• Additionally, during the dose-escalation portion and if appropriate in the expansion phase of the study, the Sponsor may modify subject enrolment into various cohorts that have not begun enrolling yet such that ENPP1 and/or cGAS baseline expression level in the subject's tumor must be available and may guide enrolment eligibility for the study
• Have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study drug (female subjects of childbearing potential who are not surgically sterilized or postmenopausal). If the urine test is positive, or cannot be confirmed as negative, a serum pregnancy test will be required.
• Demonstrate adequate organ function: hematological, renal, hepatic, coagulation parameters and obtained within 14 days prior to the first study treatment
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two highly effective contraceptive methods that result in a combined failure rate of \< 1% per year during the treatment period and for at least 120 days after the last dose of study treatment or as instructed by the package insert of the chosen co-medication.
• For male subjects: Agree that during the period specified above, men will not father a child. Male subjects must remain abstinent (refrain from heterosexual intercourse with women of childbearing potential), must be surgically sterile (e.g., vasectomy) or use contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 120 days after the last dose of study treatment.

You may not qualify if:

• Use of any systemic anti-cancer therapy (including radiotherapy, chemotherapy, targeted therapy or immunotherapy) within 2 weeks prior to first dose of RBS2418 unless such therapy is being administered in combination with RBS2418 per protocol and has been approved by the Sponsor; 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:
• 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.
• 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
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
• Known hypersensitivity allergy or contraindication to any investigational product components administered as part of the combination therapy.
• 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.

Sponsors & Collaborators

• Riboscience, LLC.: lead

Study Sites (14)

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

RECRUITING

University of Arizona

Tucson, Arizona, 85724, United States

RECRUITING

Stanford Cancer Institute

Palo Alto, California, 94305, United States

RECRUITING

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404, United States

RECRUITING

Christiana Care Health Services

Newark, Delaware, 19713, United States

RECRUITING

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

RECRUITING

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

RECRUITING

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21224, United States

RECRUITING

American Oncology Partners of Maryland

Bethesda, Maryland, 20817, United States

RECRUITING

Ichan School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

COMPLETED

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37235, United States

RECRUITING

Tranquil Research

Webster, Texas, 77598, United States

WITHDRAWN

NEXT Virigina

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Riboscience Chief Medical Officer

  Riboscience, LLC.

  STUDY DIRECTOR

Central Study Contacts

Riboscience Clinical Trials

CONTACT

‪(415) 754-3182‬; clinicaltrials@riboscience.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The dose escalation phase (Part A) employed a standard 3+3 design to identify dose-limiting toxicities (DLTs), establish the maximum tolerated dose (MTD, if observed), determine dose levels that can achieve Ctrough levels in excess of target inhibition EC90, and determine the recommended doses of RBS2418, both as monotherapy and in combination with pembrolizumab, for further evaluation. The Part A goals have been achieved, and Part A has been completed. Part B is in progress to explore the safety and preliminary efficacy of RBS2418 at selected dose levels as monotherapy and in combination with pembrolizumab or other approved anti-cancer therapies. Treatment Group A-1: RBS2418 Dose Escalation (Monotherapy) COMPLETED Treatment Group A-2: RBS2418 plus Pembrolizumab Dose Escalation (Combination Therapy) COMPLETED Treatment Group B: RBS2418 as Monotherapy or in combination with investigator-selected approved anticancer therapy.

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: March 8, 2022
• Study Start: July 11, 2022
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)