Mucosal Melanoma

Researchers are studying a new cancer treatment called [212Pb]VMT-Alpha-NET for tumors that have somatostatin receptors (SSTRs) on their surface. These tumors include those found in the lungs, head and neck, digestive tract, kidneys, and adrenal glands. The study focuses on people with tumors that have spread and cannot be removed by surgery. The goal is to find the highest safe dose of this drug and evaluate its safety and effects on these cancers. The treatment involves giving [212Pb]VMT-Alpha-NET through a vein on the first day of each 8-week cycle, for a total of four cycles. Some participants will also receive a related imaging drug, [203Pb]VMT-Alpha-NET, a few days before the first two cycles to track where the drug travels in the body using scans. After each dose, participants will stay in the hospital for a few nights and have weekly blood tests during each cycle. Participants will have physical exams, blood and urine tests, heart function tests, and imaging scans before and during the study. Researchers will monitor safety, drug effects, and tumor response through scans, lab tests, and questionnaires. Follow-up visits will continue for up to six years after the last treatment to check on long-term outcomes and overall health.

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 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 studying an investigational drug called [225Ac]Ac-A9-3408 in adults with melanoma that cannot be removed by surgery or has spread to other parts of the body. The study aims to find out the side effects of this drug and identify the highest safe dose. It also examines how well the drug shrinks melanoma tumors and measures how much of the drug reaches normal organs and tumors. Participants receive an intravenous injection of the investigational drug once every 6 weeks, for up to 6 doses. Before treatment, they are given a single intravenous dose of the diagnostic agent [68Ga]Ga-A9T-3202 during screening. The study includes two groups: a dose escalation phase to find the recommended dose and a dose expansion phase to further evaluate safety and effectiveness at that dose. During the trial, participants visit the doctor's office regularly for checkups, scans, and tests, including PET scans to measure drug uptake and tumor response. Researchers monitor side effects from the first treatment until the end of the study and assess tumor responses up to one year after enrollment. The study also tracks how the drug distributes in the body and its effects on organs. Total participation may last several months depending on the treatment cycles received.

Researchers are evaluating whether combining sacituzumab govitecan with cetuximab is an effective and safe treatment for people with recurrent or metastatic head and neck squamous cell cancer (HNSCC) who have progressed after first or second-line systemic therapy. This phase II study focuses on patients with advanced disease not suitable for curative surgery or radiation, including cancers arising from the sinuses, nasal cavity, oral cavity, oropharynx, hypopharynx, and larynx. The trial is sponsored by Memorial Sloan Kettering Cancer Center. Participants will receive sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, combined with cetuximab, an EGFR antagonist. Treatment will be given to patients with measurable disease who have shown progression after prior therapies including anti-PD(L)1 agents. The study includes patients with confirmed or pending HPV status for oropharynx cancers. No placebo or masking is used in this trial. During the study, participants will be monitored up to two years to assess the objective response rate, measuring how well tumors respond to the combination therapy. Researchers will regularly evaluate disease status, blood counts, kidney and liver function, pregnancy status, and overall health. Safety and side effects will be closely monitored to understand the treatment's impact. The study includes detailed eligibility and exclusion criteria to ensure participant safety and appropriateness for the therapy.

Researchers are evaluating treatments for patients with BRAF-V600 mutant melanoma that has spread to the brain. This phase II trial compares two combinations: encorafenib, binimetinib, and nivolumab versus ipilimumab and nivolumab. The study aims to determine which approach is more effective at shrinking and controlling brain metastases, and it also examines survival, response rates, and treatment safety. Patients are randomly assigned to one of two treatment groups. One group takes encorafenib daily by mouth, binimetinib twice daily by mouth, and receives nivolumab through an intravenous (IV) infusion every 28 days. The other group receives nivolumab IV every cycle and ipilimumab IV over 30 minutes during the first four cycles, with cycles repeating every 21 days initially, then every 28 days. Treatment continues unless disease worsens or side effects become unacceptable. Participants undergo brain MRI scans before enrollment and throughout the study to assess tumor response using specific criteria. After completing treatment, patients are followed every six months for two years, then yearly up to three years. The study collects tissue, blood, spinal fluid, and stool samples for future research. Researchers monitor progression-free survival as the main outcome, along with overall survival, response rates, and treatment side effects.

Researchers are investigating the combination of axitinib and nivolumab as a treatment for people with advanced or metastatic mucosal melanoma that has not received prior treatment. This study aims to evaluate whether using these two drugs together can better target proteins that help cancer cells survive and grow compared to using them separately. This is a phase 2 trial focusing on unresectable locally advanced or metastatic mucosal melanoma. Participants will receive nivolumab intravenously every 4 weeks along with axitinib taken orally twice daily. If the disease progresses but the patient tolerates treatment well, additional therapies may be added depending on progression type. For local or limited progression, stereotactic body radiation therapy (SBRT) will be given, and for more widespread progression or prior radiation sites, ipilimumab will be added intravenously every 3 weeks for up to four doses. The maximum duration for combined nivolumab and axitinib therapy is 104 weeks. During the study, patients will be regularly monitored through imaging to measure tumor response and other clinical assessments. The primary outcome measured is the best objective response within one year. Patients’ blood tests and organ functions will be evaluated to ensure safety, and those who progress on the initial treatment may be screened to join the triplet therapy phase. The total duration and timing of treatments and follow-ups will be carefully tracked throughout the trial.

Radiotherapy-Induced Oropharyngeal Mucositis (RIOM) is a common and distressing side effect experienced by patients with head and neck tumors during radiotherapy. This study aims to explore the use of exhaled breathomics—specifically analyzing volatile organic compounds (VOCs)—to diagnose and predict RIOM. The goal is to develop a non-invasive and early detection model that could help improve symptom management and personalize treatment for affected patients. The study involves collecting breath samples from patients with confirmed head and neck tumors who are undergoing radiotherapy or chemoradiotherapy. These samples will be analyzed using breath detection technology to identify specific VOCs that may serve as biomarkers for RIOM. The research will focus on validating this diagnostic and predictive model throughout the treatment period. Participants will be monitored for different grades of oral mucositis caused by radiotherapy, with assessments lasting up to one year. The study will record the onset and duration of mucositis symptoms. Researchers will evaluate the breath samples alongside clinical observations to understand the relationship between VOCs and mucositis severity. This observational study does not involve treatment changes but focuses on detailed data collection and follow-up.

Researchers are evaluating whether combining anti-LAG3 and anti-PD-1 drugs is more effective than anti-PD-1 alone in patients with high-risk melanoma who have detectable circulating tumor DNA (ctDNA) after surgery. This phase II study focuses on patients with stage 2B to 4 melanoma following definitive surgery. The study aims to understand if the combination treatment can better clear molecular residual disease, potentially lowering the risk of cancer recurrence. Participants will be randomly assigned to one of two groups: one receiving Opdualag (a combination of anti-LAG3 and anti-PD-1) and the other receiving Nivolumab (anti-PD-1 alone). Both treatments are given through intravenous infusion every four weeks. The randomization accounts for different melanoma stages to balance groups. About 270 patients will be screened to find at least 54 with detectable ctDNA who will proceed with treatment and follow-up. Throughout the study, participants will have their ctDNA levels monitored to assess clearance at 12 months after starting treatment. Researchers will also track recurrence-free survival at 12 and 36 months and monitor any treatment-related side effects for up to six years. Patients will undergo imaging scans and laboratory tests to ensure no detectable disease at the start and to evaluate their health during treatment. The study lasts several years, allowing thorough observation of long-term outcomes and safety.

Researchers are evaluating the effectiveness of the microneedling technique combined with topical silymarin application in treating gingival hyperpigmentation. This study compares this method with conventional scalpel and diode laser treatments to determine any clinical or aesthetic advantages. It also aims to identify any medical issues participants may experience when using topical silymarin. Participants will be divided into three groups: one receiving scalpel de-epithelization, another treated with a diode laser device, and the third undergoing microneedling with the Dr.Pen ULTIMA - A6 needle tip, followed by topical application of silymarin for ten minutes. The laser uses a wavelength of 980 nm with a 320-micron tip, while microneedling involves repetitive punctures at various speeds and needle arrangements. During the study, researchers will monitor gingival pigmentation recurrence over six months and record post-operative pain on days 1, 3, 5, and 7 after treatment. The study includes assessments of clinical and aesthetic outcomes to evaluate the treatments. Participants will be observed for any adverse effects, especially related to silymarin use, throughout the follow-up period.