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

Overview

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.

Interventions

• Drug RBS2418
  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.
• Drug Placebo
  Placebo to Match RBS2418

Primary outcome measures

• Progression Free Survival [Time frame: From randomization until the first radiographic documentation of objective progression or death from any cause, assessed up to 2 years.]
• Overall Survival [Time frame: From randomization until death from any cause, assessed up to 2 years.]

Secondary outcome measures (2)

• Duration of Response (DOR) [Time frame: From initial response to disease progression or death, assessed up to 2 years.]
• Disease Control Rate (DCR) [Time frame: From randomization to end of treatment or disease progression, assessed up to 2 years.]

Eligibility criteria

Inclusion criteria

• 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).

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 2 centers

• Christiana Care — Newark
• Community Clinical Trials — Kingwood

Vietnam · 2 centers

• Tam Anh TP. Ho Chi Minh General Hospital — Ho Chi Minh City
• Tam Anh, Ha Noi General Hospital — Hà Nội

Puerto Rico · 1 center

• Pan Oncology — San Juan

Identifiers

NCT: NCT06824064 · RBS2418-2001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗