SX-682 / Syntrix - LARVOL DELTA

Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer (clinicaltrials.gov) - P1/2 | N=120 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Enrollment open • Adenoid Cystic Carcinoma • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hypopharyngeal Cancer • Laryngeal Cancer • Nasopharyngeal Carcinoma • Non-Adenoid Cystic Carcinoma • Oncology • Oral Cancer • Oropharyngeal Cancer • Otorhinolaryngology • Prostate Cancer • Salivary Gland Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer (clinicaltrials.gov) - P1/2 | N=120 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P1/2 trial • Adenoid Cystic Carcinoma • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hypopharyngeal Cancer • Laryngeal Cancer • Nasopharyngeal Carcinoma • Non-Adenoid Cystic Carcinoma • Oncology • Oral Cancer • Oropharyngeal Cancer • Otorhinolaryngology • Prostate Cancer • Salivary Gland Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

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 | Sponsor: 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 • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD4 • MSI

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=50 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Enrollment open • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4 • MSI

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=50 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P1/2 trial • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4 • MSI

SX-682 and Atezolizumab for the Treatment of Advanced or Metastatic, Recurrent Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=32 | Recruiting | Sponsor: University of Washington | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CXCL8 • RET • ROS1

SX-682 and Atezolizumab for the Treatment of Advanced or Metastatic, Recurrent Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=32 | Not yet recruiting | Sponsor: University of Washington | Initiation date: Jun 2026 ➔ Sep 2026

Checkpoint inhibition • Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CXCL8 • RET • ROS1

SX-682 and Atezolizumab for the Treatment of Advanced or Metastatic, Recurrent Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=32 | Not yet recruiting | Sponsor: University of Washington | Initiation date: Mar 2026 ➔ Jun 2026

Checkpoint inhibition • Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CXCL8 • RET • ROS1

SX-682 and Atezolizumab for the Treatment of Advanced or Metastatic, Recurrent Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=32 | Not yet recruiting | Sponsor: University of Washington

Checkpoint inhibition • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CXCL8 • RET • ROS1

A Neoadjuvant Study of Tislelizumab and SX-682 for Resectable Pancreas Cancer (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

New P2 trial • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Neoadjuvant Study of Tislelizumab and SX-682 for Resectable Pancreas Cancer (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2026 ➔ May 2026 | Initiation date: Dec 2022 ➔ May 2023 | Trial primary completion date: Dec 2026 ➔ May 2026

Trial completion date • Trial initiation date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Neoadjuvant Study of Tislelizumab and SX-682 for Resectable Pancreas Cancer (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Neoadjuvant Study of Tislelizumab and SX-682 for Resectable Pancreas Cancer (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2026 ➔ Sep 2026 | Trial primary completion date: May 2026 ➔ Sep 2026

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Neoadjuvant Study of Tislelizumab and SX-682 for Resectable Pancreas Cancer (clinicaltrials.gov) - P2 | N=25 | Active, not recruiting | Sponsor: Lei Zheng | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Neoadjuvant Study of Tislelizumab and SX-682 for Resectable Pancreas Cancer (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Lei Zheng | Active, not recruiting ➔ Recruiting | Trial completion date: Sep 2026 ➔ Dec 2028 | Trial primary completion date: Sep 2026 ➔ Dec 2027

Enrollment open • Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Development in treating leptomeningeal Metastases (EANO 2026) - "Our results demonstrate that the Cxcl1/Cxcr2 signaling axis mediates LM growth and identifies a potential actionable intervention to improve response to pCSI and halt LM progression. This work is currently in translation in the form of a clinical trial: A Phase Ib Trial of SX-682 (CXCR1/2 inhibitor) Combined with Proton Craniospinal Irradiation for Patients with Leptomeningeal Disease."

Brain Cancer • Oncology • Solid Tumor • CXCL1 • CXCR1 • CXCR2

Safety and efficacy of first-in-class CXCR1/2 inhibitor SX-682 in combination with pembrolizumab (pem) in patients (pts) with metastatic melanoma (mMEL) with disease progression on anti–PD-1 therapy. (ASCO 2024) - P1 | "SX-682 combined with pem had a tolerable safety profile and activity reflected by objective responses and clinically meaningful disease control in heavily pretreated mMEL pts with progression on anti-PD-1 and anti–CTLA-4."

Clinical • Combination therapy • IO biomarker • Metastases • Hematological Disorders • Melanoma • Neutropenia • Oncology • Solid Tumor • BRAF • CD8 • CXCR1 • CXCR2

A Study of SX-682 in Combination With Proton Craniospinal Irradiation (pCSI) in People With Leptomeningeal Disease (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P1 trial • BRAF • CTCs

A phase I/II trial of a CXCR1/2 inhibitor in combination with anti-PD-1 for circulating tumor DNA (ctDNA) positive & refractoryRAS-mutated microsatellite stable (MSS) colorectal cancer (AACR 2023) - P1/2 | "The primary objectives are to determine safety profile, recommended phase 2 dose, clinical activity & 6m ctDNA clearance rate in CRC pts with MRD following 6m of SX-682 + Nivolumab on Arm B. Translational analyses include correlations of clinical outcomes with genomic and immune biomarkers from paired tissue and plasma samples. Clinical trial information: NCT04599140."

Circulating tumor DNA • Combination therapy • IO biomarker • P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CXCL3 • CXCR1 • CXCR2 • IRF2 • KRAS

Tumor-associated neutrophils in lung adenocarcinoma: from mechanisms to therapeutic targeting. (PubMed, Front Immunol) - "Furthermore, we evaluate current therapeutic strategies targeting TANs, such as CXCR1/2 inhibitors (SX-682, Navarixin), PAD4 inhibitors (Cl-amidine), NET-degrading enzymes (DNase I), TGF-β inhibitors (Galunisertib), and myeloid modulators, with a focus on LUAD-specific preclinical and clinical evidence. Major challenges, including off-target toxicity, infection risk, and the lack of predictive biomarkers, are discussed. By bridging mechanistic insights with translational opportunities, this review provides a framework for developing neutrophil-targeted combination therapies to overcome immunotherapy resistance in LUAD."

IO biomarker • Journal • Review • Infectious Disease • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CXCR1 • CXCR2 • IFNG • TGFB1

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 | Active, not recruiting | Sponsor: University of Rochester | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

SYNERGY-201: Study of SX-682 Plus Enzalutamide in Men With ARPI-Resistant Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=53 | Recruiting | Sponsor: Syntrix Biosystems, Inc. | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Antibacterial and anti-virulence activity of the repurposed agent SX-682 against Staphylococcus aureus. (PubMed, BMC Microbiol) - "Collectively, these findings highlight the considerable antibacterial and antibiofilm efficacy of SX-682 against S. aureus, supporting its potential as a promising therapeutic candidate for preventing and treating S. aureus infections."

Journal • Infectious Disease • CXCR1

Overcoming ICI resistance with CXCR1/2 antagonism in advanced HCC (AACR 2025) - "Finally, to understand the consequences of IL-8 inhibition via CXCR1/2 antagonism, we utilized a syngeneic murine HCC model (RIL-175 in female C57BL/6) treated with medicated SX-682 (anti-CXCR1/2) alone and in combination with intraperitoneal injections of anti-PD1+anti-VEGF. The final clinical cohort included 41 patients with advanced HCC. Patients were predominantly male (82.9%) with Barcelona Clinic Liver Cancer (BCLC) stage C disease (75.6%) who received treatment with atezolizumab + bevacizumab (51.2%)... Consistent with prior reports in other solid tumors, high plasma IL-8 concentration was associated with inferior survival on ICI based regimens in HCC. We hypothesize that IL-8 signaling promotes M2 macrophage polarization and in turn results in reduced effector T cell infiltration in the TiME. These results provide rationale for targeting the CXCR1/2 signaling axis in advanced HCC."

Metastases • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • AFP • CD8 • CXCL8 • CXCR1 • IL10 • IL6 • MRC1

Pygo2 deletion stimulates tertiary lymphoid structure formation and forms the cornerstone for a quadruple combination immunotherapy of prostate cancer (AACR 2025) - "Our study further consolidates Pygo2 as a valid and promising therapeutic target in combination immunotherapy of prostate cancer. The quadruple combination immunotherapy composed of Pygo2 inhibition, androgen deprivation therapy, SX682 and ICB demonstrates superior preclinical efficacy and should be further investigated for its clinical implications."

IO biomarker • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CXCR1 • IDO1 • PTEN • SMAD4