Trials / Active Not Recruiting

Active Not RecruitingNCT04599140

SX-682 and Nivolumab for the Treatment of RAS-Mutated, MSS Unresectable or Metastatic Colorectal Cancer, the STOPTRAFFIC-1 Trial

Phase Ib/II Trial of SX-682 in Combination With Nivolumab for Refractory RAS Mutated (RAS) Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC) (STOPTRAFFIC-1)

Status: Active Not Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 51 (actual)

Sponsor: M.D. Anderson Cancer Center · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase Ib/II trial studies the side effects and best dose of SX-682 that can be given alone and in combination with nivolumab in treating patients with RAS-Mutated, microsatellite stable (MSS) colorectal cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). SX-682 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving SX-682 alone and together with nivolumab may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVE: I. To determine the safety profile of CXCR1/2 Inhibitor SX-682 (SX-682) alone and in combination with nivolumab in subjects with refractory RAS mutated microsatellite stable (MSS) metastatic colorectal cancer (mCRC), including the maximum dose that can be administered until adverse effects prevent further dose increases (i.e., the maximum tolerated dose \[MTD\] or recommended phase 2 dose), and the dose-limiting toxicity (DLT). SECONDARY OBJECTIVES: I. Evaluate the efficacy of SX-682 in combination with nivolumab on the basis of the objective response rate (ORR), the duration of response, and the rate of progression. II. Characterize the single-dose and multidose pharmacokinetic (PK) profile of SX-682. EXPLORATORY OBJECTIVES: I. Assess overall survival (OS). II. Explore potential biomarkers associated with pharmacodynamic and clinical response to SX-682 alone and combined with nivolumab, where the biomarker measures include, but are not limited to, tumor CMS4, gene expression, deoxyribonucleic acid (DNA) mutations (KRAS, NRAS and BRAF mutation status via ribonucleic acid \[RNA\] and DNA sequencing), IRF2 (interferon regulatory factor 2) expression, lymphocyte clonality (via sequencing), myeloid-derived suppressor cell (MDSCs), regulatory T-cells (Tregs) and CD69/CD8 T cells, and in the circulation, circulating tumor DNA (ctDNA), T- and B-cell subpopulations, neutrophils, the neutrophil-to-lymphocyte ratio (NLR), MDSCs, Tregs, the CD4:CD8 ratio, chemokines and cytokines. OUTLINE: This is a phase I, dose-escalation study of CXCR1/2 Inhibitor SX-682, followed by a phase II study. MONOTHERAPY STAGE: Patients receive SX-682 orally (PO) twice daily (BID) on days 1-21 in the absence of disease progression or unacceptable toxicity. COMBINATION STAGE: Patients receive SX-682 PO BID on days 1-56 and nivolumab intravenously (IV) over 30 minutes on days 1 and 29. Treatment repeat every 56 days weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study, patients with no have tumor response are followed up every 3 weeks for 90 days, and patients with tumor response every 3 months for up to 6 months.

Conditions

Interventions

Type	Name	Description
DRUG	CXCR1/2 Inhibitor SX-682	Given PO
BIOLOGICAL	Nivolumab	Given IV

Timeline

Start date: 2020-10-14
Primary completion: 2026-07-31
Completion: 2026-07-31
First posted: 2020-10-22
Last updated: 2026-01-22

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT04599140. Inclusion in this directory is not an endorsement.