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

Metastatic Colorectal Carcinoma Clinical Trial

Official title: 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 Recruiting

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Colonic Neoplasms
• Colorectal Neoplasms
• Metastatic Colon Adenocarcinoma
• Metastatic Colorectal Carcinoma
• Metastatic Rectal Adenocarcinoma
• Rectal Neoplasms
• Stage III Colon Cancer AJCC v8
• Stage III Rectal Cancer AJCC v8
• Stage IIIA Colon Cancer AJCC v8
• Stage IIIA Rectal Cancer AJCC v8
• Stage IIIB Colon Cancer AJCC v8
• Stage IIIB Rectal Cancer AJCC v8
• Stage IIIC Colon Cancer AJCC v8
• Stage IIIC Rectal Cancer AJCC v8
• Stage IV Colon Cancer AJCC v8
• Stage IV Rectal Cancer AJCC v8
• Stage IVA Colon Cancer AJCC v8
• Stage IVA Rectal Cancer AJCC v8
• Stage IVB Colon Cancer AJCC v8
• Stage IVB Rectal Cancer AJCC v8
• Stage IVC Colon Cancer AJCC v8
• Stage IVC Rectal Cancer AJCC v8
• Unresectable Colon Adenocarcinoma
• Unresectable Rectal Adenocarcinoma

• NCT number: NCT04599140
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Contact: Alisha Bent, MD
• Phone: (713) 380-6974
• Email: abent@mdanderson.org
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 14, 2020
• Completion date: January 31, 2025