Evaluation of RBS2418 in Patients With Advanced, Metastatic, and Progressive Colorectal Cancer

NCT06824064 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: RBS2418-2001
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 3

Brief Summary

RBS2418 is a specific immune modulator that works through the inhibition of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and is designed to lead to anti-tumor immunity by protecting endogenous 2'-3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from hydrolysis and leading to the activation of antigen-presenting cells followed by T cell activation. The hypothesis is that RBS2418 versus placebo will be generally safe, well-tolerated, immunogenic, and will lead to anti-tumor responses in adult subjects for the treatment of advanced, metastatic, and progressive colorectal cancer (CRC).

Conditions

Metastatic Colorectal Cancer; Advanced Colorectal Cancer

Keywords

Advanced, Metastatic, Progressive Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival

  Time in months from randomization until the first radiographic documentation of objective progression, as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or death from any cause

  From randomization until the first radiographic documentation of objective progression or death from any cause, assessed up to 2 years.

• Overall Survival

  Time in months from the date of randomization to the date of death from any cause

  From randomization until death from any cause, assessed up to 2 years.

Secondary Outcomes (2)

• Duration of Response (DOR)

  From initial response to disease progression or death, assessed up to 2 years.

• Disease Control Rate (DCR)

  From randomization to end of treatment or disease progression, assessed up to 2 years.

Study Arms (4)

Group A: EG+ [ENPP1 and cGAS(Cyclic GMP-AMP synthase) positive] RBS2418 plus Best Supportive Care

ACTIVE COMPARATOR

RBS2418: 200 mg (2 RBS2418 capsules), PO (by mouth), BID (twice a day) plus Best Supportive Care

Drug: RBS2418

Group B: EG+ (ENPP1 and cGAS positive) Placebo plus Best Supportive Care

PLACEBO COMPARATOR

Placebo: 2 placebo capsules, PO, BID plus Best Supportive Care

Drug: Placebo

Group C: EG- (ENPP1 and/or cGAS negative) RBS2418 plus Best Supportive Care

ACTIVE COMPARATOR

RBS2418: 200 mg (2 RBS2418 capsules), PO, BID plus Best Supportive Care

Drug: RBS2418

Group D: EG- (ENPP1 and/or cGAS negative) Placebo plus Best Supportive Care

PLACEBO COMPARATOR

Placebo: 2 placebo capsules, PO, BID plus Best Supportive Care

Drug: Placebo

Interventions

RBS2418 DRUG

RBS2418 is a specific immune modulator that works through the inhibition of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and is designed to lead to anti-tumor immunity by protecting endogenous 2'-3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from hydrolysis and leading to the activation of antigen-presenting cells followed by T cell activation.

Group A: EG+ [ENPP1 and cGAS(Cyclic GMP-AMP synthase) positive] RBS2418 plus Best Supportive Care; Group C: EG- (ENPP1 and/or cGAS negative) RBS2418 plus Best Supportive Care

Placebo DRUG

Placebo to Match RBS2418

Group B: EG+ (ENPP1 and cGAS positive) Placebo plus Best Supportive Care; Group D: EG- (ENPP1 and/or cGAS negative) Placebo plus Best Supportive Care

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age on the day of signing informed consent.
• Male and female subjects with advanced, metastatic, progressive CRC who have received, been ineligible for, intolerant to, or declined all approved standard of care (SOC) therapies for metastatic CRC, as per local SOC treatment regimens. Additionally, subjects must have documented PD based on two scans performed within 2 to 4 months of study initiation.
• Have histologically or cytologically confirmed CRC diagnosis based on pathology report.
• Willing to submit a pre-treatment tissue sample (archival, or fresh tissue if archival is not available).

You may not qualify if:

• Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy, systemic immunotherapy, or radiation therapy within 2 weeks prior to the first dose of study treatment; or if subject has not recovered (i.e., ≤ to Grade 1 or returned to baseline level) from AEs 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 the first dose of study treatment.
• 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.
• Malignancies other than indications open for enrollment within 3 years prior to Day 1, except for those with negligible risk of metastasis or death treated with expected curative outcome, undergoing active surveillance, or treatment-naïve for indolent tumors.

Sponsors & Collaborators

• Riboscience, LLC.: lead
• Tam Anh Research Institute: collaborator

Study Sites (3)

Community Clinical Trials

Kingwood, Texas, 77339, United States

RECRUITING

Tam Anh TP. Ho Chi Minh General Hospital

Ho Chi Minh City, Ho Chi Minh City, 70000, Vietnam

RECRUITING

Tam Anh, Ha Noi General Hospital

Hà Nội, 10000, Vietnam

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Riboscience Clinical Trials

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2025
• First Posted: February 13, 2025
• Study Start: January 17, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); VN (2)