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Melanoma Stage IIIPhase 1NCT03161431

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

A Phase 1 study testing SX-682 and Pembrolizumab in people with Melanoma Stage III and Melanoma Stage IV, run by Syntrix Biosystems, Inc. at 6 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma Stage III, Melanoma Stage IV
What is being tested?
SX-682 and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
6 sitesUnited States
Study dates
12 Jun 2019to Jun 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • After signing the ICF and HIPAA Authorization, subjects will be evaluated for study eligibility during the Screening Period (no more than 28 days before study drug administration) according to the following further inclusion/exclusion criteria:
  • 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.
  • Women of childbearing potential (WOCBP) must use method(s) of contraception (as will be explained in detail) while on study and for 4 months after the last dose of SX-682 or pembrolizumab. A WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over age 45 in the absence of other biological or physiological causes.
  • Women under the age of 62 with a history of being postmenopausal must have a documented serum follicle stimulating hormone, (FSH) level > 40 mIU/mL.
  • Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
  • Women must not be breastfeeding.
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year while on study and for a period at least 6 months after the last dose of study drug.
  • Women who are not of childbearing potential and azoospermic men do not require contraception.

Who cannot join

  • Target Disease Exceptions
  • Active brain metastases or leptomeningeal metastases are eligible if the treating physician determines that immediate CNS specific treatment is unlikely to be required before trial screening/enrollment. Subjects with treated/stable brain metastases are also eligible. An MRI is not required to rule out brain metastases or leptomeningeal metastases. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
  • Ocular melanoma is excluded (mucosal melanoma is acceptable).
  • Medical History and Concurrent Diseases
  • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results. Specifically:
  • Subjects with active, non-infectious pneumonitis.
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  • Subjects with interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
  • Subjects with clinically significant heart disease that affects normal activities.
  • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
  • Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Use of other investigational drugs (drugs not marketed for any indication) within 30 days before study drug administration.
  • Use of QT prolonging drugs (per their approved label) must be stopped at least two (2) weeks before the start of SX-682 dosing and suspended for the length of the trial, unless in the judgment of the investigator an alternative non-prolonging substitute cannot be found, and the drug is absolutely medically necessary (if applicable contact Syntrix medical monitor for further guidance on enhanced ECG monitoring).
  • Subjects who have had major surgery in the past 4 weeks. h) Subjects who have received a live-virus vaccine within 30 days before study drug administration.
  • Physical and Laboratory Test Findings
  • Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • ECG demonstrating a QTcF interval >470 msec or patients with congenital long QT syndrome.
  • Allergies and Adverse Drug Reaction
  • History of allergy to study drug components.
  • History of severe hypersensitivity reaction to any monoclonal antibody
  • Sex and Reproduction Status
  • WOCBP who are pregnant or breastfeeding.
  • Women with a positive serum or urine pregnancy test at enrollment or prior to administration of study medication.
  • Other Exclusion Criteria
  • Prisoners or subjects who are involuntarily incarcerated, or other vulnerable populations (study is exempt from 45 CFR 46 Subparts B, C, and D).
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • MD Anderson

    Houston, Texas, 77030

  • University of Miami

    Miami, Florida, 33136

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Wilmot Cancer Institute - University of Rochester

    Rochester, New York, 14642

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
SX-682, Pembrolizumab
Keywords
Immunotherapy, Chemokine receptor blockade, Myeloid-derived suppressor cells
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SX-682Drug

    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)

  • PembrolizumabBiological

    Also called KEYTRUDA

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

Study groups in NCT03161431
Study groupRoleWhat they receive
Monotherapy: SX-682 dose escalationExperimentalEscalating 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.
Receives: Drug: SX-682
Combination therapy: SX-682 dose escalation with pembrolizumabExperimentalSX-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.
Receives: Drug: SX-682; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

  3. 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).

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

  4. 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.

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

  5. Progression free survival

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

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

  6. Overall survival

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

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

Secondary outcomes (6)

  1. SX-682 dose limiting toxicities (DLTs) during monotherapy

    Number of participants experiencing DLTs during monotherapy stage

    Measured: Up to 21 Days in 21 day Cycle 1.

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

    Number of participants experiencing DLTs during combination therapy stage

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

  3. Adverse events during Monotherapy Stage

    Number of participants experiencing clinical or laboratory adverse events (AEs) including infections and neutropenia.

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

  4. Adverse events during combination Therapy Stage

    Number of participants experiencing clinical or laboratory adverse events (AEs) including infections and neutropenia.

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

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

    Blood samples will be collected before and after the first dose SX-682 during Monotherapy Stage and Combination Therapy Stage. The Cmax will be determined.

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

  6. SX-682 steady-state pharmacokinetic parameters during SX-682 monotherapy and SX-682 and pembrolizumab combination therapy

    Blood samples will be collected before and after the morning dose of SX-682 on Day 15 of cycle 1 during monotherapy and combination therapy. The Cssmax will be determined.

    Measured: Morning dose of day 15 of Cycle 1 of monotherapy stage and combination therapy stage.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 May 2017
  2. Study start12 Jun 2019
  3. Primary completionAug 2026 (estimated)
  4. Study completionJun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
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.
Masking
None (open label)
Enrolment
77 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03161431
Sponsor's protocol ID
Syntrix-SX682-Melanoma-101
Other IDs
R44CA217591
Status last verified
Dec 2025
First submitted
16 May 2017
Last updated
23 Dec 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SX-682 and Pembrolizumab in people with Melanoma Stage III and Melanoma Stage IV, run by Syntrix Biosystems, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 23 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

SX-682 Maximum Tolerated Dose (MTD) during Monotherapy Stage (time frame: Up to 21 Days in 21 day Cycle 1 of Monotherapy Stage.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03161431.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2025.

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