Clinical trial NCT06824064: Evaluation of RBS2418 in Patients with Advanced, Metastatic, and Progressive Colorectal Cancer
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study of RBS2418 Plus Best Supportive Care (BSC) in Subjects with Advanced, Metastatic, and Progressive Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Advanced Colorectal Cancer
Keywords: Advanced, Metastatic, Progressive Colorectal Cancer
Lead sponsor: Riboscience, LLC.
Sponsor class: INDUSTRY
Collaborators: name: Tam Anh Research Institute
First posted: 2025-02-13
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed description: In this Phase 2a study, subjects must have failed, been unable to tolerate, or declined to take known standard-of-care (SOC) therapies. Subjects must have measurable disease per RECIST 1.1, an Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1 or 2, and predicted life expectancy of greater or equal to 3 months.

Up to approximately 150 subjects will be enrolled and will receive therapy as part of their respective treatment group. Subjects will receive study treatment of RBS2418 or Placebo to Match plus Best Supportive Care with a treatment period consisting of 21-day cycles up to two years or until there is progressive disease (PD), death, withdrawal, or study completion, whichever comes first.

Adverse events (AEs) will be monitored throughout the study and graded in severity according to the guidelines outlined in the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. AEs will be collected until up to 30 days after the end of treatment or until resolution, whichever comes first. Serious Adverse Events (SAEs) will be collected for 90 days after the end of treatment, or if the subject initiates new anti-cancer therapy, then 30 days after the end of treatment, whichever is earlier.

Eligibility criteria: Inclusion Criteria:

1. At least 18 years of age on the day of signing informed consent.
2. 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.
3. Have histologically or cytologically confirmed CRC diagnosis based on pathology report.
4. Willing to submit a pre-treatment tissue sample (archival, or fresh tissue if archival is not available).

Exclusion Criteria:

1. 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.
2. Subjects with evidence of rapid progression on prior therapy resulting in rapid clinical deterioration.
3. 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.

Primary outcomes:
measure: Progression Free Survival
timeFrame: From randomization until the first radiographic documentation of objective progression or death from any cause, assessed up to 2 years.
measure: Overall Survival
timeFrame: From randomization until death from any cause, assessed up to 2 years.
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: From initial response to disease progression or death, assessed up to 2 years.
measure: Disease Control Rate (DCR)
timeFrame: From randomization to end of treatment or disease progression, assessed up to 2 years.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Ho Chi Minh
country: Vietnam
facility: Tam Anh TP. Ho Chi Minh General Hospital
state: Ho Chi Minh City
city: Ha Noi
country: Vietnam
facility: Tam Anh, Ha Noi General Hospital
Study officials:
References: