SX-682 in combination with Nivolumab for ctDNA positive colorectal cancer

Colorectal Cancer
Benny Johnson, DO
MD Anderson Cancer Center


STOPTRAFFIC-1 is an ongoing phase I/II study assessing the experimental drug, SX-682, in patients with refractory RAS-mutated microsatellite stable (MSS) metastatic colorectal cancer. In collaboration with the NCI/SPORE program, Gateway will support the proposed “Arm B” of the study. This arm will assess colorectal cancer patients who are found to have positive circulating tumor DNA (ctDNA) after metastasectomy in patients with stage IV colorectal cancer and after chemotherapy with stage III colorectal cancer. Patients with positive ctDNA have microscopic residual tumor cells which results in poor survival outcomes with nearly 100% of patients experiencing disease recurrence. Tumor cells release certain proteins that bind to the protein receptors CXCR1 and CXCR2. This results in an increase in myeloid-derived suppressor cells. The high amount of myeloid-derived suppressor cells in the tumor microenvironment results in immunosuppressive “cloak” effectively hiding the tumor from immune cells. SX-682 targets CXCR1/2 preventing the increase in myeloid-derived suppressor cells and the resulting immunosuppressive “cloak”. By removing the “cloak”, it is thought that drugs that enhance the immune system, such as nivolumab – a drug that targets PD-1 and prevents cancer cells from evading the immune system – will have a synergistic effect. The researchers hypothesize that the combination of SX-682 and nivolumab in patients with ctDNA will eradicate any residual cancer cells resulting in ctDNA clearance and will increase the length of time before the cancer returns.

Trial Registration: Identifier: NCT04599140