Dapansutrile + Pembrolizumab for Melanoma

Overseen By Emily Bolch

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: April Salama, M.D.

Must not be taking: Cytotoxic chemotherapy

Disqualifiers: Ocular melanoma, Active CNS metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with melanoma that has not responded to previous PD-1 inhibitor treatments. The researchers aim to determine a safe dosage of dapansutrile (an experimental treatment) when combined with pembrolizumab (a PD-1 inhibitor) and to evaluate the effectiveness of this combination. Suitable participants have melanoma that cannot be surgically removed, have previously received a PD-1 inhibitor, and have experienced cancer progression after that treatment. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop or adjust it, as the trial excludes participants on these treatments.

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

Research has shown that dapansutrile, when used alone, is generally safe in the short term and works by reducing inflammation in the body. However, information on its long-term safety when used by itself is not yet available.

Researchers are studying the safety of combining dapansutrile with pembrolizumab. Pembrolizumab is already used to treat cancer, and its safety profile is well-established. The ongoing research aims to find the best dose of dapansutrile to use with pembrolizumab by checking for side effects and assessing patient tolerance.

Early results suggest that the treatment is generally well-tolerated, but researchers continue to test different doses to confirm this. The main goal is to ensure the combination is safe while effectively treating melanoma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about dapansutrile combined with pembrolizumab for melanoma because it offers a unique approach to treatment. Unlike most current options that focus solely on targeting cancer cells, dapansutrile works by reducing inflammation through its novel mechanism as an NLRP3 inflammasome inhibitor. This is particularly promising since inflammation plays a significant role in cancer progression. When combined with pembrolizumab, a well-known immune checkpoint inhibitor, this combination could potentially enhance the immune system's ability to fight melanoma more effectively than existing therapies.

What evidence suggests that dapansutrile + pembrolizumab might be an effective treatment for melanoma?

This trial will evaluate the combination of dapansutrile and pembrolizumab for treating melanoma that doesn't respond to PD-1 treatments. Research has shown that dapansutrile reduces tumor size and improves survival in mice. Pembrolizumab is already known to help the immune system fight various cancers. This combination aims to enhance that effect, especially when melanoma resists other treatments. Although more research is needed, these early results are promising for this difficult-to-treat cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

April Salama

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for adults with advanced melanoma that didn't respond to previous anti-PD-1/PD-L1 therapy. They must have measurable disease, adequate organ function, and no other recent cancer treatments or active infections. Participants need a performance status of 0-2 and can't be pregnant or breastfeeding. Those with certain health conditions like immunodeficiency, pneumonitis, or CNS metastases are excluded.

Inclusion Criteria

My melanoma diagnosis was confirmed through lab tests.

My cancer got worse within 6 months after my last anti-PD-1/L1 treatment.

My side effects from cancer treatment are mild, except for hair loss or hormone issues.

Exclusion Criteria

I had another cancer but was treated successfully and have been cancer-free for 2 years.

I have had chemotherapy for melanoma before joining this study.

I have a history of Hepatitis B or an active Hepatitis C infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Selection

Part 1 involves dose selection to evaluate safety and tolerability of dapansutrile + pembrolizumab, starting with dapansutrile monotherapy followed by combination therapy.

4 weeks

Multiple visits for dose escalation and monitoring

Dose Expansion

Part 2 assesses preliminary efficacy of dapansutrile + pembrolizumab with a 14-day lead-in period of dapansutrile monotherapy at the RP2D.

6 weeks

Regular visits every three weeks for pembrolizumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapansutrile
• Pembrolizumab

Trial Overview The study tests Dapansutrile in combination with Pembrolizumab on patients whose melanoma resisted PD-1 inhibitors. It has two parts: finding the best dose (with up to 1000 mg BID of Dapansutrile) and then expanding the trial at this dose to assess effectiveness against advanced melanoma.

How Is the Trial Designed?

Group I: Dose Selection Experimental Treatment 2 Interventions

Dapansutrile starting at 500 mg PO BID plus Pembrolizumab 200 mg IV every three weeks. Dose escalation is planned to a maximum of 1000 mg BID of dapansutrile + pembrolizumab.

Group II: Dose Expansion Experimental Treatment 2 Interventions

Dapansutrile at the RP2D plus Pembrolizumab 200 mg IV every three weeks

Who Is Running the Clinical Trial?

April Salama, M.D.

Lead Sponsor

Trials

1

Recruited

30+

Olatec Therapeutics LLC

Industry Sponsor

Trials

10

Recruited

1,100+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[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]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent locally advanced or metastatic Merkel cell carcinoma (MCC) based on a study of 50 patients, showing an overall response rate of 56% and a complete response rate of 24%.

The treatment demonstrated promising durability, with 96% of responding patients maintaining their response for over 6 months, and 54% for over 12 months, although common side effects included fatigue, pain, and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Accelerated Approval of Pembrolizumab for Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma. Bradford, D., Demko, S., Jin, S., et al.[2021]

Pembrolizumab, an anti-PD-1 antibody used for treating malignant pleural mesothelioma, can cause serious side effects such as minimal change disease (MCD), which was identified in a 62-year-old patient who developed nephrotic syndrome and acute renal failure after treatment.

The patient's symptoms improved significantly after discontinuing pembrolizumab and starting steroid treatment, highlighting the importance of monitoring renal function and recognizing potential autoimmune reactions in patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-associated minimal change disease in a patient with malignant pleural mesothelioma. Bickel, A., Koneth, I., Enzler-Tschudy, A., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a real-life study of 125 patients with advanced melanoma treated with pembrolizumab, the median overall survival was 16.9 months, which indicates a significant benefit, but lower than the efficacy seen in clinical trials.

While 82% of patients experienced adverse events, the safety profile was comparable to that observed in the KEYNOTE-006 clinical trial, suggesting that pembrolizumab is generally safe for use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring real-life utilization of pembrolizumab in advanced melanoma using the Portuguese National Cancer Registry. Borges, FC., Ramos, C., Ramos, A., et al.[2021]

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]

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]

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 phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04971499

A Study of Dapansutrile Plus Pembrolizumab in Patients ... Part 2 (Dose Expansion) is designed to assess preliminary efficacy of dapansutrile + pembrolizumab in PD-1 resistant melanoma. Once all patients in Part 1 have ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12308841/

Barriers to the successful treatment of melanoma - PMC Large-scale clinical trials incorporating novel targeted therapy combinations have been unsuccessful in significantly improving outcomes ...

3. biospace.com biospace.com/olatec-therapeutics-announces-the-completion-of-first-dose-cohort-in-an-innovative-trial-investigating-olatec-s-nlrp3-inhibitor-dapansutrile-and-merck-s-keytruda

Olatec Therapeutics Announces the Completion of First ... Moreover, reduction in tumor volumes in dapansutrile treated mice had increased survival when compared to untreated mice. Furthermore, data ...

4. delta.larvol.com delta.larvol.com/Products/?ProductId=6aad129f-cd23-4c92-bd6b-dacb1408c09b

dapansutrile (OLT1177) / Olatec Therap Delicious. June 02, 2025. A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma (clinicaltrials.gov) - P1/2 | N=26 ...

5. clinicaltrials.eu clinicaltrials.eu/inn/dapansutrile/

Dapansutrile – Application in Therapy and Current Clinical ... This article explores the ongoing research into dapansutrile's safety and effectiveness for diseases like gout, heart failure, diabetes, and COVID-19. We'll ...

6. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Dapansutrile_UPDATE2_%28drug_in_development%29.pdf

Dapansutrile (OLT1177) This NLRP3 inflammasome inhibitor has oral bioavailability and good short-term safety, but no long-term data. It reduces IL-1β mediated peripheral inflammation ...