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    DRUG:

    SX-682

    i
    Other names: SX-682, SX 682, SX682
    Company:
    Syntrix
    Drug class:
    CXCR2 antagonist, CXCR1 antagonist
    Related drugs:
    15d
    Phase I/II Study of the Combination Immunotherapy Regimen: SX-682, TriAdeno Vaccine, Retifanlimab and IL-15 Agonist N-803 (STAR15) for Metastatic Colorectal Cancer (mCRC) (clinicaltrials.gov)
    P1/2, N=60, Recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2028 --> Oct 2030 | Trial primary completion date: Oct 2025 --> Oct 2027
    Trial completion date • Trial primary completion date
    |
    Zynyz (retifanlimab-dlwr) • SX-682 • Anktiva (nogapendekin alfa inbakicept-pmln)
    2ms
    The Interleukin-8-CXCR1/2 Axis as a Therapeutic Target in Peritoneal Carcinomatosis. (PubMed, Curr Oncol)
    IL-8 targeting agents such as monoclonal antibodies (BMS-986253) and small-molecule inhibitors (SX-682, AZD5069, navarixin) have shown efficacy in mitigating tumor growth and improving the efficacy of immune checkpoint inhibitors. In this review, we discuss the influence of the IL-8/CXCR1/CXCR2 axis within the peritoneal immune environment in PC and highlight recent work using IL-8 or CXCR1/CXCR2 blockade as a therapeutic strategy for PC. Continued research into the peritoneal immune microenvironment and the development of targeted therapies are essential for improving the management and prognosis of PC, potentially enhancing antitumor immunity and patient outcomes.
    Review • Journal
    |
    IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • CXCR1 (Chemokine (C-X-C motif) receptor 1) • CXCR2 (Chemokine (C-X-C motif) receptor 2)
    |
    SX-682 • AZD5069 • BMS-986253 • navarixin (MK-7123)
    3ms
    Combined treatment with CDK4/6, CDK2, and CXCR1/2 inhibitors effectively halts the growth of BRAF wild-type melanoma tumors. (PubMed, Front Oncol)
    In this study, we evaluated the effectiveness of the CDK4/6 inhibitor, palbociclib, the CDK2 inhibitor, PF-07104091, the dual CXCR1 and CXCR2 (CXCR1/2) antagonist, SX-682, and the combination of these inhibitors for effective treatment of melanoma in preclinical models. This combination also decreased the percentage of CD8+ T cells that expressed PD-1 or TIM-3 and increased the ratio of MHCII+F4/80+ M1-like macrophages to CD206+F4/80+ M2-like macrophages. These data suggest that inhibiting CDK4/6 and CDK2, combined with antagonism of CXCR1/2, may be an effective treatment for BRAF wild-type melanoma tumors and NRAS mutant melanoma tumors that express Rb and are resistant to immune checkpoint inhibitors.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • IFNG (Interferon, gamma) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD4 (CD4 Molecule) • IL10 (Interleukin 10) • CCNA2 (Cyclin A2) • FOXP3 (Forkhead Box P3) • CXCR1 (Chemokine (C-X-C motif) receptor 1) • CXCR2 (Chemokine (C-X-C motif) receptor 2) • MRC1 (Mannose Receptor C-Type 1)
    |
    BRAF mutation • NRAS mutation • BRAF wild-type • NRAS wild-type
    |
    Ibrance (palbociclib) • SX-682 • tegtociclib (PF-07104091)
    4ms
    SX-682 and Nivolumab for the Treatment of RAS-Mutated, MSS Unresectable or Metastatic Colorectal Cancer, the STOPTRAFFIC-1 Trial (clinicaltrials.gov)
    P1/2, N=51, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    BRAF (B-raf proto-oncogene)
    |
    Opdivo (nivolumab) • SX-682
    6ms
    A Study to Evaluate the Safety and Tolerability of SX-682 in Combination With Nivolumab as a Maintenance Therapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov)
    P1, N=20, Recruiting, University of Rochester | Trial primary completion date: Jan 2026 --> Jun 2026
    Trial primary completion date
    |
    Opdivo (nivolumab) • SX-682
    6ms
    ASpiRE: Investigating SX-682 in Combination With Apalutamide in Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=78, Recruiting, Institute of Cancer Research, United Kingdom
    New P1/2 trial
    |
    apalutamide • SX-682
    9ms
    A Study to Evaluate the Safety and Tolerability of SX-682 in Combination with Nivolumab As a Maintenance Therapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov)
    P1, N=20, Recruiting, University of Rochester | Suspended --> Recruiting
    Enrollment open
    |
    Opdivo (nivolumab) • SX-682
    9ms
    SX-682 in Combination With Carfilzomib, Daratumumab-Hyaluronidase, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov)
    P1, N=15, Recruiting, Roswell Park Cancer Institute | Not yet recruiting --> Recruiting
    Enrollment open
    |
    carfilzomib • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • SX-682
    9ms
    SX-682 in Combination With Carfilzomib, Daratumumab-Hyaluronidase, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov)
    P1, N=15, Not yet recruiting, Roswell Park Cancer Institute | Trial completion date: Nov 2029 --> Apr 2030 | Trial primary completion date: Nov 2026 --> Apr 2027
    Trial completion date • Trial primary completion date
    |
    carfilzomib • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • SX-682
    10ms
    A Study to Evaluate the Safety and Tolerability of SX-682 in Combination with Nivolumab As a Maintenance Therapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov)
    P1, N=20, Suspended, University of Rochester | Trial completion date: Dec 2025 --> Dec 2026 | Recruiting --> Suspended | Trial primary completion date: Jan 2025 --> Jan 2026
    Trial completion date • Trial suspension • Trial primary completion date
    |
    Opdivo (nivolumab) • SX-682
    11ms
    SX-682 and Nivolumab for the Treatment of RAS-Mutated, MSS Unresectable or Metastatic Colorectal Cancer, the STOPTRAFFIC-1 Trial (clinicaltrials.gov)
    P1/2, N=53, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026
    Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CD69 (CD69 Molecule) • IRF2 (Interferon Regulatory Factor 2)
    |
    Opdivo (nivolumab) • SX-682
    12ms
    Inhibition of the chemokine receptors CXCR1 and CXCR2 synergizes with docetaxel for effective tumor control and remodeling of the immune microenvironment of HPV-negative head and neck cancer models. (PubMed, J Exp Clin Cancer Res)
    This study reports, for the first time, mechanistic findings through which the combination of CXCR1/2 inhibition and docetaxel chemotherapy exhibits synergy in models of HPV-negative HNSCC. These findings provide rationale for the use of this novel combination approach to treat HPV-negative HNSCC patients and for future combination studies of CXCR1/2 inhibition, docetaxel, and immune-based therapies.
    Preclinical • Journal
    |
    CD8 (cluster of differentiation 8) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • TUBB3 (Tubulin beta 3 class III) • MIR200C (MicroRNA 200c) • CXCR1 (Chemokine (C-X-C motif) receptor 1) • CXCR2 (Chemokine (C-X-C motif) receptor 2)
    |
    CXCL8 expression • miR-200-c expression
    |
    docetaxel • SX-682