Investigational Drug
SX-682
HealthScout AI Analysis
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Overview
SX-682 is an oral, small‑molecule, allosteric inhibitor of the chemokine receptors CXCR1 and CXCR2 being developed to modulate the tumor microenvironment by blocking recruitment of immunosuppressive myeloid cells and enhancing antitumor immunity. Clinical development includes combinations with PD‑1 inhibitors and other regimens across multiple tumor types. (dctd.cancer.gov)
Mechanism of action
- Target: CXCR1/2 on myeloid cells and neutrophils.
- Proposed effects: inhibits trafficking of myeloid‑derived suppressor cells (MDSCs) into tumors, reduces myeloid‑driven immunosuppression, and enhances activity of T and NK cell–directed immunotherapies. Preclinical studies showed SX‑682 reduced tumor MDSC accumulation and improved efficacy of adoptive NK‑ and T‑cell therapies. (dctd.cancer.gov)
Efficacy
Metastatic melanoma (post–anti‑PD‑1; SX‑682 + pembrolizumab, phase 1 dose‑escalation/expansion, NCT03161431; ASCO 2024 abstract):
- Among evaluable patients at the 200 mg BID SX‑682 dose, objective response rate (ORR) was 21% (4/19 partial responses); disease control rate (DCR) was 63% (12/19).
- Median overall survival was 14.7 months (95% CI, 10.5–NR) in the 200 mg cohort vs 7.4 months in ≤100 mg cohorts.
- Disease control increased with dose (0% ≤100 mg; 50% at 150 mg; 63% at 200 mg).
These data reflect activity in heavily pretreated patients who had progressed on anti‑PD‑1 and most also on anti‑CTLA‑4. (ascopubs.org)
Other ongoing early‑phase efficacy investigations (no peer‑reviewed results reported to date): - MSS, RAS‑mutated metastatic colorectal cancer: SX‑682 + nivolumab (STOPTRAFFIC‑1, phase I/II; design published as ASCO abstract). (ascopubs.org) - Maintenance therapy in metastatic pancreatic ductal adenocarcinoma: SX‑682 + nivolumab (phase 1; dose‑finding ongoing). (ascopubs.org) - Multiple myeloma: SX‑682 with carfilzomib, daratumumab‑hyaluronidase, and dexamethasone (phase 1, recruiting). (roswellpark.org)
Safety
In the melanoma phase 1 study (SX‑682 + pembrolizumab):
- Any‑grade and grade 3/4 treatment‑related adverse events occurred in 75% and 43% of patients, respectively; discontinuation due to treatment‑related AEs in 20%.
- When uncomplicated neutropenia (expected from CXCR2 inhibition) was excluded, grade 3/4 TRAEs were 25% and discontinuations 12% (e.g., rash, transaminitis).
- No infectious signal was observed. No dose‑limiting toxicities during the monotherapy run‑in; no maximum tolerated dose identified. (ascopubs.org)
Preclinical and translational data support an on‑target pharmacology of reduced MDSC trafficking without impairing T/NK cell infiltration or activation. (aacrjournals.org)
Ongoing and planned trials (selection)
- Metastatic melanoma: SX‑682 + pembrolizumab (phase 1 dose‑escalation/expansion; NCT03161431). (mycancergenome.org)
- MSS, RAS‑mutated mCRC: SX‑682 + nivolumab (STOPTRAFFIC‑1; NCT04599140). (ascopubs.org)
- Metastatic PDAC maintenance: SX‑682 + nivolumab (NCT04477343). (ascopubs.org)
- Relapsed/refractory multiple myeloma: SX‑682 + carfilzomib/daratumumab/dexamethasone (NCT06622005). (roswellpark.org)
- Additional pancreas cancer exploration: neoadjuvant tislelizumab + SX‑682 (institutional study). (npcf.us)
Further reading
- ASCO 2024 melanoma abstract (phase 1, SX‑682 + pembrolizumab). (ascopubs.org)
- NCI agent profile for SX‑682 (mechanism/overview). (dctd.cancer.gov)
- Clinical Cancer Research 2019: SX‑682 reduces MDSC trafficking and enhances NK‑cell immunotherapy (preclinical + human HNSCC samples). (aacrjournals.org)
- JCI 2019: Inhibiting MDSC trafficking with SX‑682 enhances T‑cell immunotherapy (preclinical). (pubmed.ncbi.nlm.nih.gov)
- Trial listings and designs: STOPTRAFFIC‑1 (mCRC), PDAC maintenance, melanoma phase 1. (ascopubs.org)
Notes: Human efficacy data to date are limited to early‑phase studies, with the most detailed results publicly available from a 2024 ASCO abstract in metastatic melanoma; other indications remain in dose‑finding or early expansion without peer‑reviewed outcomes reported. (ascopubs.org)
Last updated: Oct 2025
Active trials using SX-682
Found 5 active trials using this drug:
HealthScout AI summary: Men with mCRPC who have progressed on abiraterone (without prior enzalutamide/apalutamide/darolutamide or recent radionuclide therapy) receive enzalutamide plus SX-682, an oral CXCR1/2 inhibitor that blocks MDSC trafficking to modulate the tumor microenvironment. Key exclusions include liver metastases, significant CV disease, active autoimmune/infectious disease, and use of strong CYP3A4 modulators or QT‑prolonging drugs.
ClinicalTrials.gov ID: NCT06228053
HealthScout AI summary: This trial enrolls adults with metastatic colorectal cancer who have progressed on standard therapies (including post-checkpoint inhibitor for MSI-H/dMMR) to receive combination immunotherapy with retifanlimab (PD-1 inhibitor), TriAdeno vaccine (targets CEA, MUC1, brachyury), N-803 (IL-15 agonist), and SX-682 (oral CXCR1/2 inhibitor targeting myeloid-derived suppressor cell trafficking). The regimen is designed for patients with measurable disease and good performance status, including those with microsatellite stable tumors typically resistant to immunotherapy.
ClinicalTrials.gov ID: NCT06149481
HealthScout AI summary: Eligible patients are adults with treatment-naive, stage IIIC or IV NSCLC (PD-L1 ≥1%, no EGFR/ALK/ROS1/RET alterations, ECOG 0-1), who will receive a combination of pembrolizumab and SX-682, an oral CXCR1/2 inhibitor designed to block myeloid-derived suppressor cell infiltration and enhance anti-tumor immunity.
ClinicalTrials.gov ID: NCT05570825
HealthScout AI summary: Adults with metastatic pancreatic ductal adenocarcinoma who have achieved at least stable disease after ≥16 weeks of first-line chemotherapy (ECOG 0–1) receive maintenance nivolumab plus SX-682, an oral allosteric CXCR1/2 inhibitor designed to block MDSC trafficking and remodel the tumor microenvironment. Single-arm dose escalation of SX-682 (25–400 mg BID) with nivolumab 240 mg IV q2w; paired biopsies required.
ClinicalTrials.gov ID: NCT04477343
HealthScout AI summary: Adults with unresectable stage III/IV melanoma (including mucosal, excluding ocular) who have progressed on prior anti–PD-1/PD-L1 therapy receive the oral CXCR1/2 inhibitor SX‑682 (blocks myeloid-derived suppressor cell recruitment) with a short monotherapy lead‑in followed by combination with fixed‑dose pembrolizumab. Eligible patients must have measurable non‑CNS disease, ECOG 0–1, and may have treated/stable brain metastases; key risks include neutropenia.
ClinicalTrials.gov ID: NCT03161431
