Dapansutrile + Pembrolizumab for Melanoma
Recruiting in Palo Alto (17 mi)
Overseen byApril Salama
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: April Salama, M.D.
Must not be taking: Cytotoxic chemotherapy
Disqualifiers: Ocular melanoma, Active CNS metastases, Autoimmune disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase 1/2 trial will be conducted in two parts. Part 1 (Dose Selection) is designed to find the dose of dapansutrile with acceptable tolerability in combination with pembrolizumab. Part 1 will consist of up to 2 dose selection cohorts to evaluate the safety and tolerability of dapansutrile + pembrolizumab in patients with PD-1 resistant melanoma to find the recommended part 2 dose (RP2D). Part 1 will include a lead-in phase of dapansutrile monotherapy at 500 mg PO BID. At day 15, combination therapy with pembrolizumab will be initiated. Dose escalation is planned to a maximum of 1000 mg BID of dapansutrile + pembrolizumab.
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 completed 4 weeks of dapansutrile therapy, the expansion phase will start enrolling. Part 2 will also include a 14-day lead-in period of dapansutrile monotherapy at the RP2D.
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.
What data supports the effectiveness of the drug Dapansutrile + Pembrolizumab for melanoma?
Pembrolizumab, one of the drugs in the treatment, has been shown to be effective in treating advanced melanoma, with studies indicating high response rates and better outcomes compared to other treatments. It has been approved for use in patients with advanced melanoma, demonstrating its effectiveness in this condition.
12345Is the combination of Dapansutrile and Pembrolizumab safe for humans?
Pembrolizumab, also known as Keytruda, has been shown to be generally safe in humans, with common side effects including fatigue, rash, itching, and diarrhea. Less common side effects can include inflammation of the thyroid, colon, liver, and lungs. There is no specific safety data available for Dapansutrile in combination with Pembrolizumab, but Pembrolizumab alone has a favorable safety profile.
26789What makes the drug combination of Dapansutrile and Pembrolizumab unique for treating melanoma?
This treatment combines Dapansutrile, which is being explored for its anti-inflammatory properties, with Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells. The combination aims to enhance the immune response against melanoma, potentially offering a novel approach compared to using Pembrolizumab alone.
1261011Eligibility Criteria
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.
+13 more
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.
+18 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Dose SelectionExperimental Treatment2 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 ExpansionExperimental Treatment2 Interventions
Dapansutrile at the RP2D plus Pembrolizumab 200 mg IV every three weeks
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Duke Cancer CenterDurham, NC
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Who Is Running the Clinical Trial?
April Salama, M.D.Lead Sponsor
Olatec Therapeutics LLCIndustry Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
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.
Pembrolizumab: first global approval. [2021]Pembrolizumab [Keytruda(®) (US)], a humanized monoclonal antibody against the programmed death receptor-1 (PD-1) protein, has been developed by Merck & Co for the treatment of cancer. Pembrolizumab has received its first global approval for the treatment of advanced, unresectable or metastatic malignant melanoma in the US, for use in patients with disease progression after prior treatment with ipilimumab and, for BRAF V600 mutation-positive patients, a BRAF inhibitor. It is the first anti-PD-1 therapy to receive regulatory approval in the US, and is currently under regulatory review in the EU. This article summarizes the milestones in the development of pembrolizumab leading to this first approval for the treatment of malignant melanoma.
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.
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.
Monitoring real-life utilization of pembrolizumab in advanced melanoma using the Portuguese National Cancer Registry. [2021]To evaluate the effectiveness and safety of pembrolizumab use in advanced melanoma in a real-life context; and to explore the existence of an efficacy-effectiveness gap, comparing registry data with the reference clinical trial.
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.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
FDA Accelerated Approval of Pembrolizumab for Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma. [2021]On December 19, 2018, the Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA, Merck & Co. Inc., Whitehouse Station, NJ) for adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). Approval was based on Cancer Immunotherapy Trials Network protocol 9, also known as KEYNOTE-017 (NCT02267603), a multicenter, nonrandomized, open-label trial that enrolled 50 patients with recurrent locally advanced or metastatic MCC who had not received prior systemic therapy for their advanced disease. The major efficacy outcome measures were overall response rate (ORR) and response duration assessed by blinded independent central review per RECIST 1.1. The ORR was 56% (95% confidence interval: 41, 70) with a complete response rate of 24%. The median response duration was not reached. Among the 28 patients with responses, 96% had response durations of greater than 6 months and 54% had response durations of greater than 12 months. The most common adverse reactions of pembrolizumab reported in at least 20% of patients who received pembrolizumab as a single agent were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. IMPLICATIONS FOR PRACTICE: This report presents key information on the basis for the Food and Drug Administration's accelerated approval of pembrolizumab for the treatment of recurrent locally advanced or metastatic Merkel cell carcinoma, including efficacy and safety information. This approval provides patients and physicians with an additional treatment option for this aggressive and life-threatening carcinoma.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Pembrolizumab-associated minimal change disease in a patient with malignant pleural mesothelioma. [2022]Pembrolizumab is an anti- Programmed Death 1 (PD-1) antibody approved in melanoma, non-small cell lung cancer and investigated in malignant pleural mesothelioma. The most frequent immunotherapy related autoimmune reactions include dermatitis, pneumonitis, colitis, hypophysitis, uveitis, hypothyreodism, hepatitis and interstitial nephritis.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.