SX-682 + Pembrolizumab for Melanoma
Recruiting in Palo Alto (17 mi)
+5 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Syntrix Biosystems, Inc.
Must not be taking: QT prolonging drugs
Disqualifiers: Active autoimmune disease, Active pneumonitis, Active heart disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial requires that you stop taking any QT prolonging drugs (medications that can affect heart rhythm) at least two weeks before starting SX-682 and throughout the trial, unless no alternative is available and the drug is absolutely necessary. If this applies to you, discuss with the trial team for further guidance.
What data supports the effectiveness of the drug Pembrolizumab for melanoma?
Research shows that Pembrolizumab is effective in treating advanced melanoma, with better outcomes compared to another drug, ipilimumab. It has been approved for use in advanced melanoma and has been shown to improve survival rates in patients.
12345Is the combination of SX-682 and Pembrolizumab safe for humans?
Pembrolizumab, also known as KEYTRUDA, has been shown to be generally safe in humans, with common side effects including tiredness, rash, itching, and diarrhea. Some less common but serious side effects can include inflammation of the thyroid, colon, liver, and lungs. More studies are needed to fully understand the safety of combining it with SX-682.
678910What makes the drug SX-682 + Pembrolizumab unique for treating melanoma?
SX-682 combined with Pembrolizumab is unique because it pairs a novel investigational drug, SX-682, with Pembrolizumab, an established immunotherapy that blocks the PD-1 pathway to enhance the immune system's ability to fight melanoma. This combination may offer a new approach by potentially enhancing the effectiveness of Pembrolizumab through the additional action of SX-682, although specific details about SX-682's mechanism are not provided in the available research.
410111213Eligibility Criteria
Adults over 18 with advanced melanoma that has worsened after anti-PD1 therapy can join. They must understand the study, agree to follow its rules, and have a life expectancy over 12 weeks. Women who can get pregnant and men with partners who can must use contraception. People with certain health conditions or treatments are excluded.Inclusion Criteria
My condition worsened after anti-PD1 therapy without severe side effects.
Subjects must provide a signed and dated IRB/IEC approved written informed consent form (ICF) in accordance with regulatory and institutional guidelines.
The ICF and HIPAA authorization must be obtained before conducting any procedures that do not form a part of the subject's normal care.
+18 more
Exclusion Criteria
I have tested positive for HIV/AIDS.
History of allergy to study drug components.
History of severe hypersensitivity reaction to any monoclonal antibody.
+16 more
Participant Groups
The trial is testing SX-682's ability to block cells that shield cancer from our immune system in patients with metastatic melanoma, alongside pembrolizumab (an approved treatment). Initially, SX-682 alone is given for 21 days followed by up to two years of combined treatment.
2Treatment groups
Experimental Treatment
Group I: Monotherapy: SX-682 dose escalationExperimental Treatment1 Intervention
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.
Group II: Combination therapy: SX-682 dose escalation with pembrolizumabExperimental Treatment2 Interventions
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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Dana-Farber Cancer InstituteBoston, MA
Wilmot Cancer Institute - University of RochesterRochester, NY
MD AndersonHouston, TX
Massachusetts General Hospital Cancer CenterBoston, MA
More Trial Locations
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Who Is Running the Clinical Trial?
Syntrix Biosystems, Inc.Lead Sponsor
University of MiamiCollaborator
Mayo ClinicCollaborator
Dana-Farber Cancer InstituteCollaborator
Massachusetts General HospitalCollaborator
National Cancer Institute (NCI)Collaborator
M.D. Anderson Cancer CenterCollaborator
University of RochesterCollaborator
References
Pembrolizumab superior to ipilimumab in melanoma. [2017]In the first randomized trial to compare FDA-approved immune checkpoint inhibitors as first-line therapy for patients with advanced melanoma, pembrolizumab yielded significantly better treatment outcomes than ipilimumab.
Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab. [2022]Biomarkers for outcome after immune-checkpoint blockade are strongly needed as these may influence individual treatment selection or sequence. We aimed to identify baseline factors associated with overall survival (OS) after pembrolizumab treatment in melanoma patients.
Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program. [2018]The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program.
Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. [2021]To investigate the clinical application value of Pembrolizumab (PEM) in the treatment of advanced cutaneous malignant melanoma (ACMM).
Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. [2022]The programmed death 1 (PD-1) inhibitor pembrolizumab has been found to prolong progression-free and overall survival among patients with advanced melanoma. We conducted a phase 3 double-blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected, high-risk stage III melanoma.
Pembrolizumab in the management of metastatic melanoma. [2020]Pembrolizumab is a humanized IgG4 anti-PD-1 antibody that plays a major role in the treatment of advanced melanoma. Through blockade of PD-1, it leads to an increase in effector T-cell activity in the tumor microenvironment. Clinical trial outcomes for pembrolizumab in addition to pharmacokinetics, pharmacodynamics and safety of the compound are discussed in this article. Phase I trials have demonstrated safety and efficacy of pembrolizumab in advanced, pretreated melanoma patients. When compared with chemotherapy in a Phase II trial of ipilimumab-refractory patients, those treated with pembrolizumab showed superior progression-free survival. In addition, in the pivotal Phase III trial pembrolizumab improved overall survival compared with ipilimumab in patients naive to immune checkpoint inhibition. Pembrolizumab is well tolerated and has a favorable safety profile. Common adverse events are fatigue, rash, itching and diarrhea. Less frequent immune-related adverse events include hypothyroidism, colitis, hepatitis and pneumonitis.
Pembrolizumab in a BRAF-mutant metastatic melanoma patient following a severe immune-related adverse event with ipilimumab. [2017]Currently, limited data exist on the safety of pembrolizumab in patients with metastatic melanoma who have developed severe immune-related adverse events following treatment with ipilimumab. We report a 45-year-old male patient with BRAF-mutant metastatic melanoma who discontinued treatment with ipilimumab due to treatment-related grade 3 colitis and was subsequently treated with the anti-programmed cell death 1 protein (PD-1) antibody pembrolizumab. He has been on treatment with pembrolizumab for more than 20 months with no major toxicities and has achieved an objective partial response, which is ongoing.
Public Adverse Event Data Insights into the Safety of Pembrolizumab in Melanoma Patients. [2020]Immune checkpoint inhibition represents an important therapeutic option for advanced melanoma patients. Results from clinical studies have shown that treatment with the PD-1 inhibitors Pembrolizumab and Nivolumab provides improved response and survival rates. Moreover, combining Nivolumab with the CTLA-4 inhibitor Ipilimumab is superior to the respective monotherapies. However, use of these immunotherapies frequently associated with, sometimes life-threatening, immune-related adverse events. Thus, more evidence-based studies are required to characterize the underlying mechanisms, towards more effective clinical management and treatment monitoring. Our study examines two sets of public adverse event data coming from FAERS and VigiBase, each with more than two thousand melanoma patients treated with Pembrolizumab. Standard disproportionality metrics are utilized to characterize the safety of Pembrolizumab and its reaction profile is compared to those of the widely used Ipilimumab and Nivolumab based on melanoma cases that report only one of them. Our results confirm known toxicological considerations for their related and distinct side-effect profiles and highlight specific immune-related adverse reactions. Our retrospective computational analysis includes more patients than examined in other studies and relies on evidence coming from public pharmacovigilance data that contain safety reports from clinical and controlled studies as well as reports of suspected adverse events coming from real-world post-marketing setting. Despite these informative insights, more prospective studies are necessary to fully characterize the efficacy of these agents.
Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. [2022]We aimed to characterize the safety profile of pembrolizumab in advanced melanoma patients at our center to better reflect 'real-world' data on anti-PD-1 inhibitors.
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. [2022]Immunotherapy targeting the PD-1 axis has activity in several tumour types. We aimed to establish the activity and safety of the PD-1 inhibitor pembrolizumab in patients with untreated brain metastases from melanoma or non-small-cell lung cancer (NSCLC).
Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]Pembrolizumab (MK-3475) is a monoclonal antibody that binds to the PD-1 receptor on T cells and prevents binding to its ligands PD-L1 and PD-L2. Blocking this receptor frees T cells from the inhibitory effects of PD-L1 and allows them to mediate antitumor effects against cancer cells. In a large Phase I study of 411 patients with melanoma, high durable response rates over a range of doses and schedules have been shown with very little toxicity. A Phase III study of pembrolizumab comparing two schedules of administration with the current standard treatment with the anti-CTLA-4 monoclonal antibody is in progress. Combinations with other checkpoint inhibitors as well as other anticancer agents are also being evaluated. Approval of pembrolizumab for the treatment of melanoma is expected.
Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. [2022]The programmed death 1 (PD-1) pathway limits immune responses to melanoma and can be blocked with the humanized anti-PD-1 monoclonal antibody pembrolizumab.
Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006. [2022]Antitumor activity of ipilimumab or BRAF ± MEK inhibitors (BRAFi ± MEKi) following pembrolizumab administration in melanoma is poorly characterized.