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

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new drug called RBS2418, alone or with pembrolizumab, for patients with advanced tumors who haven't responded to other treatments. The drug works by boosting the body's natural defenses to better recognize and destroy cancer cells.

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.

What makes the drug RBS2418 unique for cancer treatment?

RBS2418 is unique because it targets the ENPP1 enzyme, which is involved in insulin signaling and glucose metabolism, potentially offering a novel approach to cancer treatment by affecting cellular processes differently than traditional therapies. ^{1 2 3 4 5}

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 1 Intervention

After dose escalation phase is completed in both monotherapy and combination therapy setting (A-1 and A-2), an expansion treatment group will be enrolled, and subjects (n=20- 40) will be treated with a fixed dose of RBS2418 to be selected by the Sponsor in consultation with the SRC and after reviewing the totality of the dose escalation data both as monotherapy and combination therapy.

Group II: Treatment Group A-2 Experimental Treatment 1 Intervention

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 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 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]

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]

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]

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]

Citations

1. England 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. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

The ENPP1 K121Q polymorphism determines individual susceptibility to the insulin-sensitising effect of lifestyle intervention. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

SGK3 mediates INPP4B-dependent PI3K signaling in breast cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

In Vivo Role of INPP4B in Tumor and Metastasis Suppression through Regulation of PI3K-AKT Signaling at Endosomes. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

ENPP1 affects insulin action and secretion: evidences from in vitro studies. [2021]