RBS2418 for Cancer

Recruiting at 18 trial locations

Overseen By Riboscience Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Riboscience, LLC.

Must not be taking: Immunomodulators, Immunosuppressants

Disqualifiers: Rapid progression, Uncontrolled pain, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

164 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RBS2418, an ENPP1 inhibitor, to determine if it can enhance the immune system's ability to fight cancer. Researchers are evaluating RBS2418 both alone and with other cancer treatments to assess its effectiveness against advanced or hard-to-remove tumors. The trial seeks individuals with advanced cancer who have not responded to standard treatments. Participants will assist researchers in determining the optimal use of this new therapy. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires that you stop any approved anti-cancer therapy, including chemotherapy, targeted small molecule therapy, or radiation therapy, at least 2 weeks before starting the trial. Additionally, you must not have taken systemic immunomodulating agents within 4 weeks or systemic immunosuppressive medication within 2 weeks prior to the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that RBS2418, whether used alone or with pembrolizumab, is generally safe and well tolerated. Studies have found that even at high doses, up to 800 mg twice a day, patients did not experience severe side effects that would limit the dosage. This suggests the drug might be safe for people.

For those considering joining a trial, these findings are important. They demonstrate that RBS2418 has been tested in previous patients with advanced cancers and did not cause serious problems at the doses studied. This indicates a good chance it could be a safe option for new participants as well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer?

RBS2418 is unique because it offers a potentially novel approach to cancer treatment by combining with pembrolizumab, an established immunotherapy drug, or as a monotherapy. Unlike traditional treatments that might focus on chemotherapy or radiation, RBS2418 allows for flexible dosing increments, starting at 100 mg and potentially increasing up to 800 mg BID, which may help tailor treatment to individual patient needs. Researchers are excited about its potential to enhance cancer treatment effectiveness through this innovative dosing strategy and its combination with other cancer therapies, which could lead to better patient outcomes.

What evidence suggests that this trial's treatments could be effective for cancer?

Research shows that RBS2418 could be a promising cancer treatment. It targets an enzyme called ENPP1, linked to tumor growth. RBS2418 increases certain molecules, like cGAMP and ATP, which help the immune system fight cancer. In this trial, participants in Treatment Group A-1 will receive RBS2418 alone, while those in Treatment Group A-2 will receive RBS2418 with pembrolizumab, a type of immunotherapy. Early studies showed that using RBS2418 alone or with pembrolizumab improved outcomes for some cancer patients, especially those with hard-to-treat tumors. Importantly, no serious side effects appeared with RBS2418, making it a potential new option for treating advanced cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Riboscience Chief Medical Officer

Principal Investigator

Riboscience, LLC.

Are You a Good Fit for This Trial?

Adults with advanced, inoperable or metastatic tumors who've tried all standard treatments without success can join. They must have a life expectancy of at least 3 months, be able to perform daily activities (with some limitations), and provide consent. Pregnant women are excluded, as well as those with severe allergies to certain drugs or uncontrolled cancer symptoms.

Inclusion Criteria

Have histologically or cytologically confirmed cancer diagnosis based on pathology report

My blood, kidney, liver, and clotting tests are all within normal ranges.

I can care for myself and am up and about more than 50% of my waking hours.

Exclusion Criteria

History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins

I am on treatment for active HIV or my HIV is not under control.

I haven't taken any immune system affecting drugs in the last 4 weeks or before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

1 visit (in-person)

Dose Escalation

Participants receive ascending doses of RBS2418 as monotherapy or in combination with pembrolizumab to identify the fixed dose for the expansion phase

Variable, up to 2 years

Visits every 3 weeks

Expansion

Participants receive a fixed dose of RBS2418 as determined by the dose escalation phase

Variable, up to 2 years

Visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days for AE monitoring, 90 days for SAE monitoring

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• RBS2418

Trial Overview RBS2418 is being tested for its ability to boost the body's immune response against tumors by affecting cellular compounds like cGAMP and ATP. This trial will explore RBS2418 alone or combined with pembrolizumab in patients whose cancers haven't responded to standard care.

How Is the Trial Designed?

Group I: Treatment Group B Experimental Treatment 3 Interventions

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

Group II: Treatment Group A-2 (Completed) Experimental Treatment 2 Interventions

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

Group III: Treatment Group A-1 (Completed) Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Riboscience, LLC.

Lead Sponsor

Trials

3

Recruited

210+

Oncobay Clinical, Inc

Collaborator

Trials

1

Recruited

60+

Published Research Related to This Trial

INPP4B expression is decreased in primary non-metastatic colorectal cancer stem-like cells (CR-CSLCs) but increased in highly metastatic CR-CSLCs, indicating its role in cancer progression.

Overexpressing INPP4B inhibits self-renewal and chemoresistance in non-metastatic CR-CSLCs while promoting these traits in metastatic CR-CSLCs, suggesting that INPP4B could be a dual therapeutic target for managing colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

INPP4B exerts a dual function in the stemness of colorectal cancer stem-like cells through regulating Sox2 and Nanog expression. Yang, L., Ding, C., Tang, W., et al.[2020]

In breast cancer, oncogenic mutations in the PIK3CA gene lead to the activation of SGK3, a protein kinase that plays a crucial role in tumor growth and invasion, independent of the traditional Akt pathway.

The study reveals that INPP4B enhances SGK3 activation while suppressing Akt phosphorylation, suggesting that both INPP4B and SGK3 contribute to tumorigenesis in breast cancers with PIK3CA mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGK3 mediates INPP4B-dependent PI3K signaling in breast cancer. Gasser, JA., Inuzuka, H., Lau, AW., et al.[2022]

The study found that the ENPP1 protein, particularly the Q121 variant, significantly impairs insulin receptor activation and insulin signaling in liver and muscle cells, leading to reduced glucose uptake and metabolism.

In beta-cells, the Q121 variant of ENPP1 also severely affects insulin secretion and cell survival, indicating that it plays a critical role in the development of insulin resistance and related metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ENPP1 affects insulin action and secretion: evidences from in vitro studies. Di Paola, R., Caporarello, N., Marucci, A., et al.[2021]

In a study of 1,563 participants at risk for type 2 diabetes, the K121Q SNP in the ENPP1 gene did not show a direct association with obesity or baseline insulin sensitivity, but it significantly influenced changes in insulin sensitivity during a 9-month lifestyle intervention.

Carriers of the minor allele of K121Q had a reduced improvement in insulin sensitivity after lifestyle changes, suggesting that this genetic variant may help predict how well individuals respond to lifestyle interventions aimed at reducing diabetes risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ENPP1 K121Q polymorphism determines individual susceptibility to the insulin-sensitising effect of lifestyle intervention. Müssig, K., Heni, M., Thamer, C., et al.[2021]

Loss of INPP4B in mice with partial PTEN loss leads to the development of aggressive and metastatic follicular-like thyroid cancer, highlighting its critical role as a tumor suppressor in thyroid oncogenesis.

INPP4B functions by inhibiting AKT2 activation in early endosomes, which is essential for controlling tumor growth and metastasis, demonstrating a unique mechanism of action distinct from PTEN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Role of INPP4B in Tumor and Metastasis Suppression through Regulation of PI3K-AKT Signaling at Endosomes. Li Chew, C., Lunardi, A., Gulluni, F., et al.[2018]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02250-6/fulltext

665P Safety, PK, immune activation, and clinical outcomes ... ... RBS2418 correlated with improved clinical outcomes in immunotherapy-unresponsive cold tumors. RBS2418 safety, PK, PD and efficacy data with a data cutoff of ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2577

Completed phase 1a dose escalation study of the first oral ... Conclusions: The Ph1a dose escalation study with oral RBS2418 alone, and with pembrolizumab has been completed. All doses were safe and well ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT381771

First-in-human experience using RBS2418, an oral ENPP1 ... Results: All evaluated dose levels of RBS2418 in combination with pembrolizumab were found to be safe and well tolerated. No dose-limiting drug-related ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05270213?term=AREA%5BInterventionSearch%5D(rbs2418)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=1

Evaluation of RBS2418 in Subjects With Advanced ... RBS2418 has the potential to be an important therapeutic option for subjects both as monotherapy and in combination with other cancer treatments including ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2597

Correlation of baseline ENPP1 and cGAS expression in ... RBS2418, a first-in-class, potent ENPP1 inhibitor, is evaluated as monotherapy and combination with pembrolizumab in advanced/metastatic solid tumors.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03001-6/fulltext

1025MO Preliminary safety, pharmacokinetics and ... Oral RBS2418 alone or with pembrolizumab has been safe and well tolerated at all dose levels studied to date in the ongoing dose escalation study. The PK ...