Investigational Drug
SX-682
TrialFetch AI Analysis
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Overview
SX-682 is an investigational, orally administered small molecule being developed primarily as an immunotherapy adjunct in cancer. It is an allosteric inhibitor of the chemokine receptors CXCR1 and CXCR2. The most substantive human results reported to date come from a phase 1 study combining SX-682 with pembrolizumab in previously treated metastatic melanoma; the findings remain preliminary and have been reported as a conference abstract rather than a full peer-reviewed clinical publication. (s3.amazonaws.com)
Mechanism of action
CXCR1/2 signaling promotes the migration of immunosuppressive neutrophils and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) into tumors. By blocking these receptors, SX-682 is intended to reduce myeloid-cell trafficking into the tumor microenvironment and facilitate infiltration and activity of cytotoxic T cells or natural killer cells. Preclinical studies found that SX-682 enhanced checkpoint-inhibitor and adoptive-cell therapies, although SX-682 alone had limited or model-dependent direct antitumor activity. (pmc.ncbi.nlm.nih.gov)
Efficacy
In the phase 1 NCT03161431 trial, 51 patients with metastatic melanoma that had progressed during prior anti–PD-1 therapy received SX-682 plus pembrolizumab. Most were heavily pretreated: 73% had previously received combined anti–PD-1/anti–CTLA-4 therapy. (s3.amazonaws.com)
Among 19 response-evaluable patients receiving SX-682 at 200 mg twice daily:
- Objective response rate: 21%—four partial responses and no complete responses.
- Disease-control rate: 63%—four partial responses and eight cases of stable disease.
- Median overall survival: 14.7 months in the full 200-mg cohort, versus 7.4 months among patients receiving 100 mg or less.
These results come from a small, nonrandomized dose-escalation study and do not establish how much benefit was attributable to SX-682 rather than pembrolizumab or patient selection. (s3.amazonaws.com)
Safety
No dose-limiting toxicities or maximum tolerated dose were identified during SX-682 monotherapy. Across combination-treatment dose groups, treatment-related adverse events occurred in 75% of patients, with grade 3–4 events in 43% and treatment discontinuation in 20%. When uncomplicated neutropenia—an anticipated pharmacologic effect of CXCR2 inhibition—was excluded, grade 3–4 treatment-related events occurred in 25%, and 12% discontinued because of rash or elevated liver enzymes. No infection signal was reported. (s3.amazonaws.com)
Further reading
- Phase 1 melanoma results in the Journal of Clinical Oncology
- Preclinical study of SX-682 with T-cell immunotherapies
- Preclinical study of SX-682 with NK-cell immunotherapy
- National Cancer Institute drug description
Last updated: Sep 2026
Active trials using SX-682
Found 5 active trials using this drug:
TrialFetch AI summary: Adults with metastatic, recurrent, or unresectable stage IIIC NSCLC who progressed after platinum-doublet chemotherapy and anti–PD-1/PD-L1 therapy receive oral SX-682, an investigational CXCR1/2 inhibitor, plus subcutaneous atezolizumab, an anti–PD-L1 antibody. Patients with known EGFR mutations or ALK, ROS1, or RET fusions are excluded.
ClinicalTrials.gov ID: NCT07322341
TrialFetch AI summary: Men with metastatic castration-resistant prostate cancer that has progressed during or after abiraterone receive enzalutamide plus investigational oral SX-682, a CXCR1/2 inhibitor intended to reduce trafficking of immunosuppressive myeloid cells into tumors. Prior enzalutamide or other second-generation androgen-receptor antagonist use and current liver metastases are excluded.
ClinicalTrials.gov ID: NCT06228053
TrialFetch AI summary: Adults with previously treated, measurable metastatic colorectal cancer receive retifanlimab (anti–PD-1), a CEA/MUC1/brachyury-targeted TriAdeno vaccine, and the IL-15 agonist N-803, with or without SX-682, a CXCR1/2 inhibitor intended to limit immunosuppressive myeloid-cell trafficking. Patients with MSI-H/dMMR disease must have received prior checkpoint inhibitor therapy.
ClinicalTrials.gov ID: NCT06149481
TrialFetch AI summary: Adults with treatment-naive metastatic or recurrent NSCLC, or unresectable stage IIIC disease not amenable to curative radiation, are eligible if PD-L1 expression is ≥1%, ECOG performance status is 0–1, and there is no known EGFR, ALK, ROS1, or RET alteration. All participants receive pembrolizumab plus oral SX-682, a CXCR1/2 inhibitor intended to reduce recruitment of immunosuppressive myeloid cells.
ClinicalTrials.gov ID: NCT05570825
TrialFetch AI summary: Adults with metastatic pancreatic ductal adenocarcinoma that has not progressed after at least 16 weeks of first-line chemotherapy receive maintenance oral SX-682, an investigational CXCR1/2 inhibitor, plus nivolumab, a PD-1–blocking antibody. Patients must have ECOG performance status 0–1 and be able to undergo tumor biopsies.
ClinicalTrials.gov ID: NCT04477343
