NCT03161431

SX-682 Treatment in Subjects With Metastatic Melanoma Concurrently Treated With Pembrolizumab

A Phase 1, Open-Label, Dose-Escalation With Expansion Study of SX-682 in Subjects With Metastatic Melanoma Concurrently Treated With Pembrolizumab

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 77 (estimated)
• Sponsor: Syntrix Biosystems, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Cancers attract myeloid-derived suppressor cells (MDSCs) that prevent our own immune responses from destroying the cancer. This study will be the first study to begin to determine if the newly discovered drug SX-682 can block cancers from attracting MDSCs. This first study will enroll participants with melanoma, as melanoma cancer has been shown to be able to attract MDSCs. The study will begin to determine if SX-682 is a safe and effective treatment of melanoma. It is thought that SX-682 will block MDSCs from going to the cancer, and thus will allow a patient's own immune system to attack the cancer. The first participants enrolled in the study will receive for 21 days SX-682 as monotherapy. After 21 days participants will receive pembrolizumab therapy (an approved immunotherapy for melanoma) in combination with SX-682 for up to approximately 2 years. Once the safe dose level of SX-682 in combination with pembrolizumab is determined, the remaining participants will be enrolled at the highest safe dose level of SX-682, in combination with pembrolizumab. These participants will receive the combination therapy and be evaluated in the study for approximately 2 years.

Detailed description

Objectives The primary objective is to determine the safety profile of SX-682 alone and in combination with pembrolizumab in subjects with metastatic melanoma, including the maximum dose that can be administered until adverse effects prevent further dose increases, and the dose-limiting toxicity (DLT). The secondary objectives are to: 1) evaluate the efficacy of SX-682 in combination with pembrolizumab on the basis of the objective response rate, the duration of response, and the rate of progression; and 2) characterize the SX-682 single-dose and multidose PK profile. Exploratory objectives are to: 1) assess overall survival (OS); and 2) explore potential biomarkers associated with pharmacodynamic and clinical response to SX-682 alone and combined with pembrolizumab, where the biomarker measures include, but are not limited to, tumor myeloid-derived suppressor cells (MDSC), Tregs and CD69/CD8 T cells, and in the circulation, T- and B-cell subpopulations, neutrophils, the neutrophil-to-lymphocyte ratio (NLR), Tregs, the CD4:CD8 ratio, chemokines, cytokines, and LDH. Overview of Study Design This is a Phase 1, open-label, multi-center, dose-escalation with expansion study of twice-daily SX-682 in subjects with metastatic melanoma treated concurrently with pembrolizumab (Combination Stage) following a 21 day dose-escalation safety evaluation of SX-682 monotherapy (Monotherapy Stage). SX-682 is an oral small-molecule inhibitor of the CXCR1/2 chemokine receptors that are believed involved in MDSC-recruitment to tumor and other pro-tumoral mechanisms. Dosing of SX-682 in the Combination Stage is conditioned on ongoing concurrent treatment with pembrolizumab, and a subject who discontinues pembrolizumab may not receive further doses of SX-682.

Conditions

• Melanoma Stage III
• Melanoma Stage IV

Interventions

Type	Name	Description
DRUG	SX-682	SX-682 is an oral small molecule selective inhibitor of C-X-C Motif Chemokine Receptor 1 (CXCR1) and C-X-C Motif Chemokine Receptor 2 (CXCR2)
BIOLOGICAL	Pembrolizumab	Pembrolizumab is a humanized antibody that targets the programmed cell death 1 receptor (PD-1).

Timeline

• Start date: 2019-06-12
• Primary completion: 2026-08-01
• Completion: 2027-06-01
• First posted: 2017-05-19
• Last updated: 2025-12-23

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study