Merkel Cell Carcinoma

Researchers are evaluating MDNA11, a long-acting "beta-only" recombinant interleukin-2 designed to activate immune cells that kill cancer while minimizing activation of immunosuppressive cells. This Phase 1/2 study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of MDNA11 alone or combined with the checkpoint inhibitor pembrolizumab in patients with advanced solid tumors. The study is conducted at multiple sites with regulatory and ethical approvals and includes about 115 patients. The trial has several parts: dose escalation and expansion for MDNA11 monotherapy and for its combination with pembrolizumab. MDNA11 is given intravenously every two weeks with doses adjusted to find the recommended dose for expansion. Tumor assessments using CT or MRI scans happen every 8 weeks to monitor response until disease progression or other study-end criteria occur. Treatment may continue beyond progression under certain conditions. Participants undergo evaluations including tumor imaging, laboratory tests, and safety monitoring over up to 24 months. Researchers measure recommended dose levels, treatment-related adverse events, pharmacokinetics, immune response, and anti-tumor activity such as response rates and progression-free survival. Patients can withdraw anytime, and safety follow-up continues to understand MDNA11's effects alone and with pembrolizumab.

Researchers are evaluating ONM-501, a drug given as intratumoral injections, alone and in combination with cemiplimab, an immune checkpoint inhibitor, in patients with advanced solid tumors and lymphomas. This phase 1 study aims to find the maximum tolerated dose, minimum effective dose, and recommended dose for expansion of ONM-501. The study includes patients with various advanced cancers who have no alternative standard therapies available. The trial has three parts: monotherapy dose escalation, combination therapy dose finding, and combination therapy dose expansion. ONM-501 is given once per week for three weeks followed by three weeks off, in 21-day cycles. Cemiplimab is given intravenously every three weeks during the combination phases. Dose escalation uses special methods to gradually increase doses, and after doses are established, patients will enroll in expansion cohorts for specific tumor types. Participants will have regular assessments including monitoring for side effects, blood tests to measure drug levels, and evaluation of tumor response over up to 24 months. Researchers will track treatment-emergent adverse events, dose-limiting toxicities, and serious adverse events. Outcomes such as objective response rate, duration of response, progression-free survival, and overall survival will also be recorded. The study involves close safety monitoring and follow-up throughout the treatment and observation periods.

Researchers are evaluating KUP-101A, a drug given by intravenous infusion, in patients with certain advanced solid tumors including cutaneous melanoma, mucosal melanoma, cutaneous squamous cell carcinoma, Merkel cell carcinoma of the skin, and basal cell carcinoma of the skin. This Phase 1 trial aims to find the highest dose of KUP-101A that patients can tolerate and to assess its safety and how it behaves in the body. Researchers will also gather initial data on how well KUP-101A works for these patients. Participants will receive KUP-101A at increasing dose levels, starting from Dose level 1 up to Dose level 7, to determine the recommended dose for further studies. The drug is given through infusion into a vein. The study is not randomized or blinded, meaning all participants receive the investigational treatment. The trial will monitor patients from enrollment and during treatment to observe any side effects, dose-limiting toxicities, and laboratory test results. During the study, patients will be closely monitored for adverse events, changes in laboratory values, vital signs, and heart function using electrocardiograms (ECG). Researchers will also assess pharmacokinetic measures such as drug concentration in the blood over time and the drug's elimination half-life. Cytokine levels will be measured to understand immune responses. Safety follow-up will continue for three months after the last dose. Participation duration and visit schedules will depend on the dosing and monitoring requirements.

Researchers are evaluating a mobile health intervention designed to promote sun protection behaviors and skin examinations among Hispanics at risk for skin cancer. This study aims to assess the feasibility, acceptability, and preliminary effects of a culturally guided WhatsApp-based program compared to general physical activity and nutrition information. The study will gather insights from Hispanic community members and key stakeholders to develop the intervention and refine it through a pilot randomized controlled trial (RCT). Participants will first complete a baseline survey before being randomly assigned to either the intervention group receiving WhatsApp messages about skin cancer prevention for three months or a control group receiving information on physical activity and nutrition. After the intervention, participants will complete a post-intervention survey, followed by a six-month follow-up survey to assess longer-term behavior changes. The intervention uses a user-centered approach incorporating feedback from focus groups and interviews. Throughout the study, researchers will monitor skin cancer-related preventive behaviors such as the use of sunscreen, seeking shade, wearing protective clothing, hats, and sunglasses, as well as skin self-examination and professional skin examinations. Data will be collected at baseline, three months, and six months. The study also evaluates participant satisfaction and retention rates to inform further refinements. Total participation involves surveys and engagement via WhatsApp over a six-month period.

Researchers are studying the effects of injecting the seasonal influenza vaccine directly into cutaneous squamous cell carcinoma (CSCC) tumors before patients undergo standard Mohs excision surgery. This Phase 0, window-of-opportunity trial aims to understand if the influenza vaccine can boost the immune system's response against this type of skin cancer. The study involves adults diagnosed with CSCC who are preparing for curative surgery. Participants will receive the Fluzone influenza vaccine injected into their tumor on days 1 and 8. On day 15, they will have the standard Mohs micrographic surgery to remove the tumor, with tissue collected for analysis. Follow-up visits occur on day 21 for suture removal and day 38 to monitor recovery and any effects. During the study, participants will have blood tests, tumor measurements, and photographs taken to track changes. Researchers will assess immune cell changes, tumor size, and safety outcomes up to 38 days. The main measurement is the change in CD8+ T-cell density within the tumor. Participants will be monitored closely throughout the trial, which is expected to include 25 people.

This research aims to evaluate whether a topical 5% niacinamide cream can help prevent skin cancer in organ transplant recipients. These individuals face a significantly higher risk of developing precancerous skin growths and skin cancers due to long-term use of immune-suppressing medications. The study focuses on whether daily topical niacinamide, combined with sunscreen, can reduce actinic keratoses and new keratinocyte cancers compared to sunscreen alone in this high-risk group. Participants will be randomly assigned to one of two groups: one will apply topical 5% niacinamide cream once daily plus use SPF 30 sunscreen daily and every two hours when outdoors, while the control group will use sunscreen alone. The study lasts 12 months, with skin examinations at 6 and 12 months to assess changes in actinic keratosis counts and the development of new skin cancers. The safety, tolerability, and adherence to the niacinamide cream will also be evaluated. During the study, participants will undergo standardized skin mapping and clinical exams at 6 and 12 months. Researchers will collect data on treatment side effects, adherence, and patient experiences through structured surveys. Any suspicious lesions will be examined by a board-certified pathologist. The primary outcome is the change in actinic keratosis count, and secondary outcomes include the incidence of new non-melanoma skin cancers and product tolerability.

Researchers are evaluating the safety and effects of a study drug called CRD3874-SI in adults with advanced or metastatic malignant solid tumors, including types such as sarcoma, Merkel Cell Carcinoma, head and neck squamous cell carcinoma, adenoid cystic carcinoma, uveal melanoma, mucosal and acral melanoma, and non-small cell lung cancer. The study aims to find the highest dose of CRD3874-SI that causes only mild or manageable side effects and to learn more about how the drug is processed by the body and how the immune system responds to it. Participants receive weekly intravenous infusions of CRD3874-SI starting at a dose of 0.1 mg/kg, with dose levels increasing in phases to find the recommended dose for further study. The treatment cycles vary, with the first two cycles consisting of four weekly infusions each over 28 days, and later cycles providing three weekly infusions if the treatment is well tolerated. The trial also includes a dose expansion phase where the recommended dose and one additional active dose are tested in selected tumor types. Blood tests and tumor biopsies are performed during the study to help assess the drug's effects. During the trial, participants undergo regular evaluations including tumor biopsies (when feasible), blood tests for immune cells, and assessments of tumor response. Safety is closely monitored through side effect tracking and organ function tests. The study's main outcomes include determining the maximum tolerated dose over one year and measuring tumor response rates during dose expansion up to 48 weeks. Participation may last several months depending on treatment tolerance and disease progression, with ongoing monitoring to understand the drug's safety and activity.

Researchers are studying people with solid tumor cancers that have returned, spread, or worsened after standard treatments, or when no standard treatments are available. This study aims to find the highest dose of MQ710, a modified virus therapy, that causes few or mild side effects in these patients. The trial is an open-label, phase 1 study focusing on safety and tolerability of this treatment in solid tumors. Participants will receive MQ710 injected directly into their tumors. Some will receive MQ710 alone, while others will receive MQ710 combined with pembrolizumab, a drug given intravenously every three weeks. The study includes a dose escalation phase to find the best dose, followed by groups receiving the established doses of MQ710 alone or with pembrolizumab. During the study, participants will have regular assessments including biopsies, physical exams, and monitoring for side effects. The study will review adverse events for up to two years to evaluate safety. Participants must comply with study procedures and will be closely monitored throughout the trial period, which started in May 2023 and is expected to continue until May 2028.

Researchers are evaluating oral Alintegimod (7HP349) alone and in combination with ipilimumab, followed by nivolumab monotherapy, in patients with locally advanced or metastatic cancers who have received one or more prior therapies. This open-label Phase Ib dose escalation study is followed by a blinded, randomized multi-cohort Phase 2a comparison of combination versus reference regimens, aiming to assess safety, tolerability, and preliminary efficacy. Participants will receive Alintegimod monotherapy in escalating doses for one cycle, then Alintegimod combined with ipilimumab for four cycles, followed by nivolumab monotherapy for eleven cycles. Alintegimod is given orally as softgel capsules, while ipilimumab and nivolumab are administered intravenously. The treatment continues until the end of the study period, lasting 12 months, unless disease progression or toxicity requires early termination. Throughout the study, participants will undergo assessments including adverse event monitoring, pharmacokinetic testing, and tumor response evaluations using RECIST criteria. Researchers will measure treatment-related side effects, drug levels in the blood, progression-free survival, and overall response rates. Safety will be closely monitored over 18 months, with participants expected to attend regular visits for clinical evaluations and laboratory tests during the study duration.

Researchers are evaluating pembrolizumab, a study medicine, in Japanese pediatric participants with specific solid tumors or lymphomas and Japanese adult participants with Merkel cell carcinoma (MCC), a type of skin cancer. The study aims to understand the safety and tolerability of pembrolizumab, how different doses behave in the body over time, and how the cancer responds to the treatment. This research is conducted as a Phase I/II trial sponsored by Merck Sharp & Dohme LLC. Pediatric participants with solid tumors or lymphomas receive pembrolizumab at a dose of 2 mg/kg through an intravenous infusion every three weeks on Day 1 of each 21-day cycle, for up to 17 or 35 cycles. Adult participants with MCC receive 400 mg pembrolizumab via intravenous infusion every six weeks (42-day cycle) for up to 18 cycles. Each study arm follows its own dosing schedule and treatment duration. Participants will be closely monitored through various assessments including measuring adverse events, drug concentrations in the blood at specified cycles, and cancer response evaluations using established criteria such as RECIST 1.1 and Lugano classification. The study tracks multiple outcomes like objective response rates, duration of response, disease control, progression-free survival, and overall survival, with follow-up periods extending up to approximately 46 months. Safety and treatment tolerability are key aspects monitored throughout the study duration.