SX-682 + Pembrolizumab for Melanoma

Recruiting at 5 trial locations

Overseen By Stuart Kahn

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Syntrix Biosystems, Inc.

Must not be taking: QT prolonging drugs

Disqualifiers: Active autoimmune disease, Active pneumonitis, Active heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

77 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, SX-682, to determine if it can help fight melanoma, a type of skin cancer, by boosting the immune system's response. Melanoma often attracts cells that prevent the immune system from attacking the cancer. The study will first evaluate SX-682 alone and then in combination with pembrolizumab (an existing melanoma treatment) to assess safety and effectiveness. Individuals diagnosed with melanoma that cannot be surgically removed (stages III or IV) and who have not responded to previous treatments might be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how SX-682 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using SX-682 with pembrolizumab is generally safe and well-tolerated. In earlier studies, this combination did not cause severe side effects, and patients responded well, effectively controlling the disease.

Moreover, pembrolizumab is already approved for treating melanoma, providing reassurance about its safety. While SX-682 remains under study, current data from patients using this combination therapy is encouraging regarding safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for melanoma?

Unlike the standard treatments for melanoma, which often include immunotherapies like pembrolizumab alone, SX-682 offers a fresh approach by targeting the chemokine receptor CXCR1/2. This mechanism helps to block signals that attract immune-suppressive cells to the tumor site, potentially enhancing the body's immune response against cancer cells. Additionally, SX-682 is administered orally, making it a convenient option compared to many existing treatments that require infusion. Researchers are excited about the potential of SX-682 to work synergistically with pembrolizumab, possibly leading to improved outcomes for patients with melanoma.

What evidence suggests that SX-682 might be an effective treatment for melanoma?

Research shows that SX-682, a new drug, might help treat melanoma by stopping certain cells from protecting the cancer, potentially enabling the body's immune system to attack the cancer more effectively. In this trial, some participants will receive SX-682 alone, which studies have found to be generally safe and capable of helping control the disease. Other participants will receive a combination of SX-682 with pembrolizumab, a treatment already approved for melanoma. This combination has shown promise in further controlling the cancer. Pembrolizumab is known to improve outcomes in advanced melanoma. These findings suggest that SX-682, especially when combined with pembrolizumab, could be effective in treating melanoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Stuart Kahn, M.D.

Principal Investigator

Syntrix Biosystems

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monotherapy

Participants receive escalating doses of SX-682 as monotherapy to determine the maximum tolerated dose

3 weeks

Daily visits for dose escalation monitoring

Combination Therapy

Participants receive SX-682 in combination with pembrolizumab in 6-week cycles

Up to 2 years

2 visits per cycle (in-person for pembrolizumab infusions)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• SX-682

Trial Overview

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.

How Is the Trial Designed?

Group I: Monotherapy: SX-682 dose escalation Experimental Treatment 1 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 pembrolizumab Experimental Treatment 2 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.

Who Is Running the Clinical Trial?

Syntrix Biosystems, Inc.

Lead Sponsor

Trials

14

Recruited

810+

University of Miami

Collaborator

Trials

976

Recruited

423,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

Published Research Related to This Trial

A 45-year-old male with metastatic melanoma experienced severe immune-related adverse events from ipilimumab, leading to its discontinuation, but successfully transitioned to pembrolizumab.

After over 20 months of treatment with pembrolizumab, the patient has shown no major toxicities and has achieved an ongoing partial response, suggesting that pembrolizumab may be a safe and effective option for patients with prior severe adverse events from other immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in a BRAF-mutant metastatic melanoma patient following a severe immune-related adverse event with ipilimumab. Aya, F., Fernández-Martínez, A., Gaba, L., et al.[2017]

In a study of 655 patients with advanced melanoma, pembrolizumab showed an overall objective response rate of 33%, indicating its efficacy in treating this type of cancer.

The median overall survival for patients receiving pembrolizumab was 23 months, with a 12-month survival rate of 66%, while 14% of patients experienced severe treatment-related adverse events, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. Ribas, A., Hamid, O., Daud, A., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

In a study of 616 melanoma patients treated with pembrolizumab, specific baseline factors such as high relative eosinophil count, high relative lymphocyte count, low lactate dehydrogenase levels, and limited metastasis were linked to significantly better overall survival rates.

Patients with all four favorable factors had a one-year overall survival probability of 83.9%, while those with none had only 14.7%, highlighting the importance of these biomarkers in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab. Weide, B., Martens, A., Hassel, JC., et al.[2022]

In a study of 67 advanced melanoma patients treated with pembrolizumab, the drug demonstrated a 27% overall response rate, with 6.5% achieving complete responses, indicating its efficacy even in heavily pretreated patients.

The median overall survival for cutaneous melanoma patients was 14 months, with an 18-month survival rate of 47.1%, and importantly, there were no serious adverse events reported, highlighting the safety of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program. González-Cao, M., Arance, A., Piulats, JM., et al.[2018]

In a phase 3 trial involving 1,019 patients with resected high-risk stage III melanoma, pembrolizumab significantly improved recurrence-free survival compared to placebo, with a 1-year rate of 75.4% versus 61.0%.

While pembrolizumab was effective, it was associated with a higher rate of severe adverse events (14.7% vs. 3.4% in the placebo group), including one treatment-related death, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. Eggermont, AMM., Blank, CU., Mandala, M., et al.[2022]

Pembrolizumab (PEM) significantly improved short-term treatment effectiveness and long-term survival rates in patients with advanced cutaneous malignant melanoma compared to chemotherapy with Temozolomide, with a notable increase in one-year survival rates (53.85% vs. 40.00%).

The use of PEM did not lead to a higher incidence of adverse reactions compared to the control group, indicating that it is a relatively safe treatment option for patients with this type of melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. Fu, L., Zhang, H., Jiang, J., et al.[2021]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a phase 2 trial involving 36 patients with untreated brain metastases from melanoma or non-small-cell lung cancer (NSCLC), pembrolizumab demonstrated activity, achieving a brain metastasis response in 22% of melanoma patients and 33% of NSCLC patients, with responses being durable for most.

The treatment had an acceptable safety profile, with serious adverse events occurring in a small percentage of patients, indicating that systemic immunotherapy could be a viable option for those with untreated or progressive brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Goldberg, SB., Gettinger, SN., Mahajan, A., et al.[2022]

In a post hoc analysis of the KEYNOTE-006 study involving 555 patients with advanced melanoma, both ipilimumab and BRAF ± MEK inhibitors showed antitumor activity as subsequent therapies after pembrolizumab, with overall response rates (ORR) of 17.5% for ipilimumab and 30.5% for BRAF ± MEK inhibitors.

Patients who had not previously received BRAF ± MEK inhibitors showed a significantly higher ORR of 43.2% when treated with these agents after pembrolizumab, indicating that prior treatment status may influence the effectiveness of subsequent therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006. Long, GV., Arance, A., Mortier, L., et al.[2022]

The study confirms that PD-1 inhibitors like Pembrolizumab and Nivolumab improve response and survival rates in advanced melanoma patients, especially when combined with the CTLA-4 inhibitor Ipilimumab, which shows superior efficacy compared to monotherapies.

However, these immunotherapies are associated with significant immune-related adverse events, some of which can be life-threatening, highlighting the need for further studies to better understand their safety profiles and mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Public Adverse Event Data Insights into the Safety of Pembrolizumab in Melanoma Patients. Schaefer, A., Sachpekidis, C., Diella, F., et al.[2020]

In a randomized trial comparing FDA-approved immune checkpoint inhibitors for advanced melanoma, pembrolizumab showed significantly better treatment outcomes than ipilimumab.

This study is notable as it is the first to directly compare these two therapies as first-line treatments, highlighting pembrolizumab's potential as a more effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab superior to ipilimumab in melanoma. [2017]

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As a single agent, SX-682 increases tumor CD8+ T cell infiltration and inhibits tumor growth in mouse melanoma models. This dose-escalation with expansion trial ...

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SX-682 + Pembrolizumab for Melanoma

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The primary objective is to determine the safety profile of SX-682 alone and in combination with pembrolizumab in subjects with metastatic ...