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

NCT03161431 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: Syntrix-SX682-Melanoma-101R44CA217591
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Melanoma Stage III; Melanoma Stage IV

Keywords

Immunotherapy; Chemokine receptor blockade; Myeloid-derived suppressor cells

Outcome Measures

Primary Outcomes (6)

• SX-682 Maximum Tolerated Dose (MTD) during Monotherapy Stage

  During the Monotherapy Stage participant cohorts will be enrolled at increasing doses of SX-682. The highest SX-682 dose tested at which no more than 1 of 6 cohort participants experiences a DLT will define the SX-682 monotherapy MTD.

  Up to 21 Days in 21 day Cycle 1 of Monotherapy Stage.

• SX-682 Maximum Tolerated Dose during Combination Therapy Stage

  During the Combination Therapy Stage participant cohorts will be enrolled at increasing doses of SX-682 and a fixed pembrolizumab dose level. The highest SX-682 dose tested at which no more than 1 of 6 cohort participants experiences a DLT will define the SX-682 combination therapy MTD.

  Up to 42 Days in 42 day Cycle 1 of Combination Therapy Stage.

• The observed tumor response rate

  The percentage of participants with their best response (a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).

  Days 38-42 of each 42 day Combination Stage cycle (Cycles 1-17)

• The observed tumor response duration

  Duration of CR or PR according to RECIST v1.1 from the time of first documentation to radiologic progression or death.

  Days 38-42 of each 42 day Combination Stage cycle (Cycles 1-17)

• Progression free survival

  The time from first SX-682 dose to documented disease progression according to RECIST v1.1 or death from any cause

  Days 38-42 of each 42 day Combination Stage cycle (Cycles 1-17)

• Overall survival

  During combination stage the time from first SX-682 dose to death from any cause.

  Combination Stage cycle (Cycles 1-17) and the 90 day follow-up period after the last SX-682 dose.

Secondary Outcomes (6)

• SX-682 dose limiting toxicities (DLTs) during monotherapy

  Up to 21 Days in 21 day Cycle 1.

• SX-682 dose limiting toxicities (DLTs) during combination therapy stage

  Days 38-42 of each 42 day Combination Stage cycle (Cycles 1-17).

• Adverse events during Monotherapy Stage

  Up to 21 Days in 21 day Cycle 1 of monotherapy stage.

• Adverse events during combination Therapy Stage

  Up to 42 Days in 42 day Cycle 1-17 of Combination Therapy Stage.

• SX-682 single dose pharmacokinetic parameters during SX-682 monotherapy and SX-682 and pembrolizumab combination therapy

  SX-682 dose on Day 1 of Cycle 1 of Monotherapy Stage and Combination Therapy Stage.

Study Arms (2)

Monotherapy: SX-682 dose escalation

EXPERIMENTAL

Escalating oral doses of SX-682 (study drug) of 25, 50, 100, 200 and 400 mg twice-daily (i.e., 50, 100, 200, 400 and 800 mg total each day.

Drug: SX-682

Combination therapy: SX-682 dose escalation with pembrolizumab

EXPERIMENTAL

SX-682 will be administrated at the same dose the participant was administered in monotherapy and will be administered in a 6 week cycle that includes 2 i.v. infusions of pembrolizumab on days 1 and 22 of each cycle, for a total of up to 17 cycles. Once the highest safe dose of SX-682 in combination therapy with pembrolizumab is determined, participants will be enrolled in an expansion phase at that SX-682 dose with pembrolizumab combination therapy.

Drug: SX-682; Biological: Pembrolizumab

Interventions

SX-682 DRUG

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)

Combination therapy: SX-682 dose escalation with pembrolizumab; Monotherapy: SX-682 dose escalation

Pembrolizumab BIOLOGICAL

Pembrolizumab is a humanized antibody that targets the programmed cell death 1 receptor (PD-1).

Also known as: KEYTRUDA

Combination therapy: SX-682 dose escalation with pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written Informed Consent and HIPAA Authorization
• Subjects must have the nature of the study explained to them.
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, pharmacokinetic collections, and other requirements of the study.
• Subjects must provide a signed and dated IRB/IEC approved written informed consent form (ICF) in accordance with regulatory and institutional guidelines.
• Subjects must provide a signed and dated Health Insurance Portability and Accountability Act (HIPAA) authorization.
• The ICF and HIPAA authorization must be obtained before conducting any procedures that do not form a part of the subject's normal care.

You may not qualify if:

• Target Population
• Histologically confirmed unresectable Stage III or Stage IV melanoma as per AJCC staging system. (mucosal melanoma is acceptable).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Prior disease progression on anti-PD1 therapy (i.e., anti-PD1 or anti-PD-L1, including prior adjuvant). Prior anti-PD1 therapy must have been completed prior to first dose of SX-682, and all adverse events related to prior therapy have either returned to baseline or stabilized (other than endocrine toxicity for which medical replacement therapy is in place).
• Must have at least measurable non-CNS disease with at least 1 unidimensional measurable lesion per RECIST v1.1.
• Pre-treatment tumor tissue (i.e., archived paraffin-embedded) obtained in the metastatic setting or from an unresectable site of disease must be available for biomarker analyses. Biopsy should be excisional, incisional punch or core needle. Fine needle aspirates or other cytology samples are insufficient.
• Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration.
• Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to first dose:
• WBC \> 3000/µL Neutrophils \> 1500/ µL Platelets \> 100,000/µL Hemoglobin \> 9.0 g/dL (may have been transfused) Creatinine \< 1.5 mg/dL AST/ALT \< 2.5 X ULN for subject with no liver metastases \< 5 X ULN for subjects with liver metastases Bilirubin \< 1.5 mg/dL (unless diagnosed with Gilbert's syndrome, who can have total bilirubin \< 3.0 mg/dL) INR or PT \< 1.5 X ULN unless the subject is receiving anticoagulant therapy aPTT or PTT \< 1.5 X ULN unless the subject is receiving anticoagulant therapy
• Calculate and record creatinine clearance using the Cockcroft-Gault formula.
• No known positivity for human immunodeficiency virus (HIV) (no laboratory testing is required), no active infection with Hepatitis B or Hepatitis C.
• Life expectancy \> 12 weeks.
• Subject Re-enrollment: This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (i.e., subject has not been treated with SX-682) after obtaining agreement from the medical monitor prior to re-enrolling a subject. If re-enrolled, the subject must be re-consented.
• Age and Reproductive Status
• Men and women, ages \> 18 years of age.

Sponsors & Collaborators

• Syntrix Biosystems, Inc.: lead
• Mayo Clinic: collaborator
• Massachusetts General Hospital: collaborator
• National Cancer Institute (NCI): collaborator
• Dana-Farber Cancer Institute: collaborator
• University of Rochester: collaborator
• M.D. Anderson Cancer Center: collaborator
• University of Miami: collaborator

Study Sites (6)

University of Miami

Miami, Florida, 33136, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Wilmot Cancer Institute - University of Rochester

Rochester, New York, 14642, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Stuart Kahn, M.D.

  Syntrix Biosystems

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In this sequential model initially participant groups will enroll to receive SX-682 monotherapy for 21 days in a dose escalation phase. A 3 + 3 participant design will be used to determine the safe dose. After 21 days, at the specified dose of SX-682 monotherapy, subjects are administered combination therapy consisting of SX-682 at the same dose as used in monotherapy and standard pembrolizumab therapy. Again, a 3 + 3 participant design will be used to determine the safe dose of SX-682 in combination therapy with pembrolizumab. The next higher dose level will be enrolled only after subjects have received the current dose level safely for at least 6 weeks. Once the safe dose level of SX-682 in combination with pembrolizumab is determined, then participants will be enrolled at the highest safe dose level of SX-682, in combination with pembrolizumab, in an expansion phase.

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 19, 2017
• Study Start: June 12, 2019
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)