Phase 1/2 SX-682 CXCR1/2 inhibitor plus docetaxel microtubule inhibitor in R/M HNSCC

This National Cancer Institute (NCI) Phase 1/2 study tests SX-682, an oral small-molecule CXCR1/CXCR2 inhibitor designed to block IL-8–axis chemokine signaling that recruits pro-tumor myeloid cells, in combination with docetaxel (DTX), a taxane that inhibits microtubule dynamics and disrupts cell division. The design uses dose escalation (Arm 1) to define a recommended Phase 2 dose (RP2D), followed by expansion at the RP2D (Arm 2), with 3-week cycles: SX-682 twice daily on Days 1–11 and docetaxel IV on Day 8, for up to 6 cycles. Eligible cohorts include unresectable recurrent/metastatic head and neck squamous cell carcinoma after prior platinum and PD-1/PD-L1 therapy, advanced/metastatic/recurrent unresectable salivary gland carcinoma, and progressive metastatic castration-resistant prostate cancer (mCRPC) in the 2nd-line+ setting on ongoing androgen deprivation or after orchiectomy. The scientific angle is whether CXCR1/2 blockade can remodel an immunosuppressive tumor microenvironment and potentially reverse docetaxel resistance signals, making a conventional chemotherapy backbone work better across multiple tumor types. Today’s care in these settings is sequential systemic therapy—HNSCC typically PD-1–based therapy then taxane/cetuximab-based regimens; mCRPC commonly AR-pathway inhibitors and/or docetaxel/cabazitaxel; and salivary gland cancers often rely on chemotherapy or biomarker-directed options (e.g., HER2- or AR-targeted therapy when present)—so this explores an immunology-adjacent add-on to a familiar taxane backbone.