Wollstonecraft

Researchers are investigating if intismeran autogene combined with pembrolizumab can prevent advanced melanoma from growing or spreading. Advanced melanoma is skin cancer that has spread to other parts of the body and cannot be removed with surgery. The study aims to see if people receiving intismeran autogene with pembrolizumab live longer without their cancer worsening than those receiving placebo with pembrolizumab. This is a phase 2 clinical trial evaluating these treatments in people with first-line advanced melanoma. Participants will receive either intismeran autogene or placebo via intramuscular injection every 3 weeks for up to 9 doses about 27 weeks. All participants will also receive pembrolizumab by intravenous infusion every 6 weeks for up to 17 doses, totaling around 2 years of treatment or until their disease progresses or they stop the treatment. The study compares the experimental combination to a placebo plus pembrolizumab to better understand the effects of intismeran autogene. During the study, participants will have regular assessments to measure how long they live without the cancer growing or spreading, as well as overall response and survival up to 6 years. Researchers will monitor side effects and reasons for stopping therapy for up to 2 years. Participants will undergo scans and tumor tissue analysis for biomarker studies. The trial includes a randomized design with triple masking and aims to enroll adults aged 18 and older with advanced melanoma.

Researchers are evaluating the safety, effectiveness, optimal dose, and behavior of an investigational drug called BNT326, alone or combined with other immunotherapy agents, in adults with advanced solid tumors. This study includes patients with tumors that have either spread metastatic, returned after treatment, or progressed despite previous therapies, across various cancer types such as melanoma, lung cancer, breast cancer, gastric cancer, colorectal cancer, and cervical cancer. Participants are divided into two parts Part 1 tests BNT326 alone in different tumor-specific groups, some with dose randomization to find optimal dosing. Part 2 evaluates BNT326 alone or combined with another investigational drug called pumitamig in several cancer types, with some groups receiving randomized doses and others non-randomized treatments. Treatments are given via intravenous infusion, with some oral medications combined in Part 1. The study includes dose escalation and randomization phases, and treatment can continue for up to 24 months or until disease progression or other reasons. During the study, participants undergo screening, treatment, safety follow-up, efficacy follow-up, and long-term survival monitoring phases. Researchers assess adverse events, treatment responses, disease progression, and drug behavior in the body using clinical evaluations and laboratory tests. Follow-up assessments occur up to approximately 38 months for Part 1 and 48 months for Part 2, with continued treatment possible for those benefiting from the therapy. The study aims to gather comprehensive data on safety, dosing, and effectiveness in this patient population.

Researchers are investigating the clinical benefits of combining RP2, a genetically modified herpes simplex virus, with nivolumab, an immune checkpoint inhibitor, in adults with metastatic uveal melanoma who have not previously received immune checkpoint inhibitor therapy. This phase 23 randomized trial compares this combination against the combination of nivolumab and ipilimumab, another immune checkpoint inhibitor, to evaluate their effects on survival and disease progression. Participants will be randomly assigned to receive either RP2 plus nivolumab or ipilimumab plus nivolumab. RP2 is designed to stimulate the immune system and directly attack tumors, while nivolumab and ipilimumab work by blocking proteins that limit immune response against cancer cells. The study treatment is administered over time, with careful monitoring of safety and effectiveness. There are no placebo groups, and the trial is open-label, meaning both participants and researchers know which treatment is given. Throughout the study, participants will undergo regular assessments to evaluate overall survival and progression-free survival for up to three years after the last treatment dose. Additional evaluations include tracking response rates and disease control every 12 weeks and monitoring for any treatment-related adverse events for up to 100 days post-treatment. Blood tests, tumor biopsies, and imaging will be part of the ongoing evaluations. Participants are expected to remain engaged with the study procedures for the duration of the follow-up period to help researchers understand the treatments impact.

Researchers are evaluating treatments for patients with asymptomatic, untreated melanoma brain metastases in this phase II randomized trial. The study compares a combination of immunotherapy drugs, ipilimumab and nivolumab, given with or without stereotactic radiotherapy to the brain. This approach builds on earlier findings suggesting that combining these therapies may enhance the immune response against melanoma brain tumors and improve outcomes. Participants will receive combination treatment with ipilimumab and nivolumab according to approved dosing schedules. One group will also receive stereotactic radiotherapy to the brain within 7 days of a baseline MRI scan, while the other group will receive immunotherapy alone. Salvage therapies like surgery or radiotherapy may be used if brain disease progresses. The study aims to assess the effects of these treatments on survival, tumor response, neurocognitive function, quality of life, and side effects. During the study, participants will undergo brain MRIs, neurological and cognitive assessments, and complete quality of life questionnaires regularly. Blood, tissue, stool, and urine samples will be collected to study biomarkers related to treatment response and toxicity. Safety will be monitored through adverse event reporting. Participants will be followed for up to 10 years to evaluate neurological death rates, tumor response, survival, cognitive changes, and quality of life.

Researchers are evaluating the combination of brenetafusp IMC-F106C plus nivolumab compared to standard nivolumab regimens in people with previously untreated advanced melanoma who are HLA-A*0201-positive. This phase 3, randomized, controlled study aims to understand how these treatments perform in this specific group. The study focuses on improving progression-free survival and overall outcomes for participants with advanced melanoma. Participants are assigned to one of three groups one group receives a low dose of brenetafusp once weekly for 13 weeks, then every two weeks until Week 51, and every four weeks thereafter, along with nivolumab every four weeks another group receives a high dose of brenetafusp on the same schedule plus nivolumab the third group receives nivolumab alone or nivolumab combined with relatlimab every four weeks. The study includes a dose recommendation phase with changes made in November 2025 based on safety and efficacy data. During the study, participants undergo assessments including tumor measurements per RECIST 1.1, BRAF V600 mutation status evaluation, and performance status scoring. Researchers will monitor progression-free survival up to approximately 45 months, overall survival up to 57 months, and record adverse events, immune responses, and quality of life. The study involves regular dosing and long-term follow-up to evaluate treatment effects and safety.

This research evaluates the long-term safety and effectiveness of pembrolizumab in participants with advanced tumors or hematologic malignancies who have previously taken part in Merck pembrolizumab-based studies. This phase 3 extension study includes participants currently on treatment or in follow-up from parent trials. The study has three phases based on participants prior treatment status First Course Phase, Survival Follow-up Phase, and Second Course Phase, allowing continuation or observation depending on prior participation. Participants receive pembrolizumab alone or combined with other treatments such as standard of care therapies, lenvatinib, olaparib, MK-4280, MK-4280A, or pembrolizumab with berahyaluronidase alfa. Dosing schedules vary by phase and regimen, including intravenous infusions of pembrolizumab every 3 or 6 weeks, oral lenvatinib capsules daily, oral olaparib tablets twice daily, and other biologics administered intravenously or subcutaneously. The study allows up to 35 doses in the First Course Phase and fewer doses in the Second Course Phase, with treatment durations adjusted for crossover eligibility and combination therapies. Participants are monitored through regular treatment visits involving drug administration and follow-up assessments. Researchers evaluate overall survival up to approximately 10 years, along with progression-free survival, event-free survival, and adverse events including serious and clinically significant side effects. The study includes ongoing safety monitoring up to around 40 months post-treatment. Participants remain under observation for long-term outcomes and potential treatment effects for many years after enrollment.

Researchers are evaluating new combinations of immunotherapy for patients with resectable stage 3 cutaneous melanoma and any stage of mucosal melanoma. The study focuses on patients who can have surgery to remove all tumor deposits. The goal is to improve outcomes for patients who typically respond poorly to standard immunotherapy by testing neoadjuvant immunotherapy given before surgery to reduce recurrence. The trial tests six different immunotherapy combinations using the drugs nivolumab, relatlimab, ipilimumab, and pembrolizumab. These are given as two doses before surgery to stimulate the immune system to better attack melanoma cells. After surgery, patients may receive standard immunotherapy if the neoadjuvant treatment does not sufficiently reduce cancer cells. The study includes four phases neoadjuvant treatment, surgery, possible adjuvant therapy, and long-term follow-up for up to 10 years. Participants will undergo assessments including biomarker testing, imaging, and pathology to evaluate tumor response at six weeks. Researchers will monitor survival, recurrence, side effects, and quality of life over 10 years. The study will also explore biomarkers in blood, tumor tissue, and stool to understand treatment response. A total of 493 patients will participate in this phase II trial conducted in Australia.

This research aims to evaluate neoadjuvant therapy using a combination of two immune checkpoint inhibitors, nivolumab and relatlimab, targeting the PD-1 and LAG-3 pathways in patients with treatment-nafve, resectable stage II to IV cutaneous squamous cell carcinoma. The study is a phase 2, open-label, single-group trial designed to assess pathological response rate and recurrence-free survival compared to historical data from monotherapy with cemiplimab. It focuses on improving outcomes in this patient population by testing dual immune checkpoint inhibition before surgery. Participants will receive two doses of a fixed dose combination of nivolumab 480 mg and relatlimab 160 mg administered by infusion on days 1 and 29 before surgery. Patients who do not achieve a complete pathological response may then receive standard radiotherapy as decided by a multidisciplinary team. This neoadjuvant treatment approach aims to enhance tumor response prior to surgical removal. During the study, participants will undergo tumor biopsies, imaging assessments, and blood tests to evaluate pathological response, toxicity, and tolerability of the therapy. Outcomes measured include pathological complete response rate at week 6, recurrence-free survival over 10 years, quality of life assessments at one year, and overall survival. Safety and completion of treatment are monitored up to week 48. The total study participation includes pre-surgery treatment followed by long-term follow-up for survival and disease recurrence.

This research aims to evaluate neoadjuvant dual immunotherapy using nivolumab and relatlimab in patients with resectable stage I to stage III Merkel cell carcinoma. The study focuses on treatment-naefve patients and compares the pathological response rate and recurrence-free survival to historical data from nivolumab monotherapy. The trial is phase 2, open-label, and single-arm, conducted at a single center to explore the combined immune checkpoint inhibition of PD-1 and LAG-3 pathways. Participants will receive two doses of a fixed dose combination of nivolumab 480 mg and relatlimab 160 mg administered by infusion on days 1 and 29 before surgery. The treatment regimen is based on prior studies in melanoma patients and aims to assess the safety and efficacy of this dual checkpoint inhibition as neoadjuvant therapy. All enrolled participants will receive the same treatment, with no placebo or comparator group. During the study, participants will be closely monitored for pathological responses, toxicity, tolerability, and objective and metabolic responses at week 6 and week 24. The study will also track recurrence-free survival, event-free survival, overall survival, and patient-reported quality of life for up to 10 years. Surgical-related adverse events and treatment completion rates will be assessed, with overall study duration extending to long-term outcomes and safety follow-up.

Researchers are evaluating STX-001, a new investigational treatment delivered directly into tumors, alone or combined with pembrolizumab, in patients with advanced solid tumors. This Phase 12 open-label trial aims to assess the safety, tolerability, how the drug moves and acts in the body, and early signs of anti-tumor effects. The study includes patients with different types of advanced cancers, including specific groups for triple-negative breast cancer and melanoma. The study is divided into several parts. Phase 1 involves dose escalation of STX-001 as monotherapy and in combination with pembrolizumab, including cohorts targeting visceral lesions. Phase 2 expands dosing in patients with triple-negative breast cancer and melanoma, further evaluating STX-001 combined with pembrolizumab and selecting the recommended dose based on earlier results. Treatments are given by intratumoral injection, possibly into multiple tumor sites, with dose extensions and treatment pauses allowed, lasting up to 35 cycles over approximately 24 months. Participants will undergo assessments including safety monitoring, blood tests, tumor biopsies before and after injections, and imaging to evaluate tumor response. Researchers will track side effects, laboratory values, drug levels, immune cell activity in tumors, and anti-tumor activity up to 18 months after the last dose. The study involves multiple visits and monitoring periods to gather detailed information on the investigational treatments effects and safety.