Wollstonecraft

Researchers are studying intismeran autogene combined with pembrolizumab to see if it can stop advanced melanoma, a type of skin cancer that has spread and cannot be removed by surgery, from growing or spreading. This Phase 2 study compares this combination to pembrolizumab with a placebo, aiming to find out if the new treatment helps people live longer without cancer progression. Immunotherapy, which helps the immune system fight cancer, is a standard treatment for advanced melanoma, and intismeran autogene is designed to boost the immune response against a person's specific cancer. Participants receive either intismeran autogene or a placebo through intramuscular injection, along with pembrolizumab given as an intravenous infusion. The study is randomized, double-blind, and controlled, meaning neither participants nor researchers know who gets the active treatment or placebo. This design helps to better understand the effects of intismeran autogene when combined with pembrolizumab. During the study, researchers will monitor participants for up to about 36 months to measure progression-free survival, which means the length of time participants live without the cancer worsening. Assessments include imaging scans to track tumor changes, tumor tissue collection for biomarker analysis, and documentation of any side effects. Participants may also have their mutation status checked and will be observed for safety throughout the study period.

Researchers are evaluating the safety, effectiveness, best dose, and how the body processes (pharmacokinetics) an investigational drug called BNT326. This study includes people with advanced solid tumors that are metastatic, recurrent, or have progressed after previous treatments. The investigation is divided into two parts: Part 1 tests BNT326 alone, and Part 2 studies BNT326 alone or combined with other immunotherapy drugs, including pumitamig (BNT327). Participants have specific tumor types like melanoma, non-small cell lung cancer, breast cancer, gastric cancer, colorectal cancer, and cervical cancer, among others. In Part 1, participants receive BNT326 by intravenous infusion in various groups based on cancer type and prior treatments. Part 2 involves BNT326 given alone or with pumitamig, also by intravenous infusion, in several defined cancer groups. Some groups are randomized to receive different dose levels or combinations to find the optimal treatment plan. The study includes a screening phase, treatment phase lasting up to 24 months or until progression or unacceptable side effects, a safety follow-up, efficacy follow-up, and long-term survival monitoring, totaling about 38 months for Part 1 and 48 months for Part 2. During the study, participants undergo regular assessments including measuring tumor response using RECIST criteria, monitoring for side effects and serious adverse events up to months after treatment ends, and measuring drug levels in the blood. Researchers track treatment interruptions or discontinuations due to side effects and evaluate dose-limiting toxicities. Tumor tissue samples are required before enrollment. Safety and effectiveness data are collected throughout treatment and follow-up periods to understand how well BNT326 works alone or combined and its safety profile.

Researchers are evaluating the clinical benefits of a new treatment combination for adults with metastatic uveal melanoma who have not received immune checkpoint inhibitor therapy before. This study compares the combination of RP2, a genetically modified herpes simplex virus designed to kill tumors and stimulate the immune system, with nivolumab, an anti-PD-1 antibody, against the combination of nivolumab and ipilimumab, a CTLA-4-blocking antibody. This is a randomized, open-label study conducted in phases 2 and 3 to assess the effectiveness and safety of these treatments. Participants will receive either the RP2 and nivolumab combination or the nivolumab and ipilimumab combination. RP2 is administered directly into tumors that can be injected, while nivolumab and ipilimumab are given as biological therapies to help the immune system attack the cancer. The study includes monitoring treatment effects over time and may involve multiple injections and infusions as per the study protocol. Treatments are designed to be given to patients who have measurable tumors suitable for injection. During the study, participants will be closely followed to measure overall survival and progression-free survival for up to three years after their last dose. Researchers will conduct various assessments including tumor measurements, safety monitoring, and laboratory tests to evaluate how well the treatments work and their safety. The study requires participants to provide tumor biopsy samples and meet specific health criteria to ensure their safety and the reliability of the results.

Researchers are evaluating the use of immunotherapy drugs ipilimumab and nivolumab, with or without concurrent stereotactic radiotherapy, in patients with asymptomatic, untreated melanoma brain metastases. This phase II, open-label, randomized trial builds on previous findings that combining ipilimumab with nivolumab is more effective than nivolumab alone. The study aims to assess the impact of these treatments on neurological specific death rates at 12 months, as well as tumor response, survival, cognitive function, quality of life, and side effects. Participants will receive combination immunotherapy with ipilimumab and nivolumab at doses approved for advanced melanoma. One group will also receive stereotactic radiotherapy to brain metastases within 7 days of a planning MRI scan, while the other group will receive immunotherapy alone. At any progression of brain disease, salvage therapies like surgery or radiotherapy may be used. Treatment and follow-up include regular brain MRI scans and evaluations. Throughout the study, participants will undergo neurocognitive testing, neurological assessments, and quality of life questionnaires at baseline and every 6 to 12 weeks. Blood, tissue, stool, and urine samples will be collected for biomarker studies to understand treatment response and side effects. Adverse events will be carefully monitored, including specific attention to radionecrosis. The total participation time and continuation of treatment depend on disease progression and clinical benefit, with options for extended immunotherapy or stopping after two years.

Researchers are evaluating the effectiveness of brenetafusp (IMC-F106C) combined with nivolumab compared to standard nivolumab treatments in people who have advanced melanoma that has not been treated before. This study focuses on participants who have a specific genetic marker called HLA-A*02:01 and aims to understand how these treatments affect the progression of their cancer. The study is a phase 3, randomized, controlled trial, which helps ensure reliable comparison between the different treatment regimens. Participants in this study will receive either brenetafusp plus nivolumab or standard nivolumab regimens, which may include nivolumab alone or in combination with relatlimab. These treatments are given by intravenous infusion, with specific dosing of the drugs as concentrates for infusion. The study compares these approaches to see which is more effective in controlling the melanoma. During the study, participants will be closely monitored for disease progression and overall health. Researchers will use scans and other assessments to measure progression-free survival, which is the time participants live without their disease worsening, followed for up to about 45 months. Safety and response to treatment will be regularly evaluated to better understand the effects of the therapies over time.

Researchers are evaluating the long-term safety and effectiveness of pembrolizumab (MK-3475) in participants with advanced solid tumors or blood cancers who have previously taken part in other pembrolizumab-based studies. This phase 3 study includes participants who are either currently on treatment or in follow-up from prior parent studies. It aims to understand how well pembrolizumab works over an extended period, up to approximately 10 years, by observing overall survival and safety outcomes. The study has three phases: First Course Phase, Survival Follow-up Phase, and Second Course Phase. Participants who were receiving pembrolizumab, pembrolizumab-based combinations, or lenvatinib in their parent studies will continue treatment in the First Course Phase, completing up to 35 doses every 3 weeks or 17 doses every 6 weeks. Those in the Follow-up Phase will enter the Survival Follow-up Phase without additional treatment but will be monitored. Participants eligible for a Second Course Phase, who have not received other anticancer treatments since their prior pembrolizumab dose and meet health criteria, may receive up to 17 doses every 3 weeks or 8 doses every 6 weeks of pembrolizumab or its combinations. Some may also receive other study drugs such as olaparib, MK-4280, MK-4280A, or pembrolizumab with berahyaluronidase alfa. Participants will be involved in regular treatment visits, safety checks, and long-term monitoring for up to about 10 years to assess overall survival. Researchers will evaluate clinical outcomes, monitor any side effects, and check organ function and physical health status. The study includes detailed eligibility screening, including physical assessments and adherence to contraception requirements for women of childbearing potential. Safety follow-up is ongoing to ensure participant well-being throughout the study.

Researchers are evaluating new immunotherapy combinations in patients with stage 3 cutaneous melanoma and mucosal melanoma that can be surgically removed. The study focuses on patients who are poor responders to standard immunotherapy and aims to improve the chance that melanoma will not return after surgery. This phase II clinical trial includes three patient groups based on their melanoma type and response to previous treatments. The trial tests five different combinations of immunotherapy drugs given before surgery, called neoadjuvant treatment. These combinations include drugs such as ipilimumab, nivolumab, relatlimab, and pembrolizumab, administered in two doses over several weeks. After surgery, patients may receive standard immunotherapy if the neoadjuvant therapy does not sufficiently reduce cancer cells. The study follows patients for up to 10 years to monitor recurrence and survival. Participants will undergo surgery after the neoadjuvant treatment and receive regular follow-ups for melanoma recurrence and survival. Researchers will assess how well the new immunotherapy combinations destroy melanoma cells before surgery by measuring pathological response rates at week 6. Additional evaluations include side effects, quality of life, and biomarker research using blood, tumor tissue, and stool samples. The total study duration includes treatment, surgery, adjuvant therapy if needed, and long-term follow-up.

Researchers are evaluating a new treatment approach for patients with treatment-naefve, resectable stage II to IV cutaneous squamous cell carcinoma. This phase 2, open-label clinical trial studies the effect of dual immune checkpoint inhibition targeting PD-1 and LAG-3 pathways on the pathological complete response rate and recurrence-free survival. The goal is to see if this dual therapy improves outcomes compared to historical data from cemiplimab monotherapy in a similar patient group. Participants receive neoadjuvant immunotherapy using a fixed dose combination of Nivolumab 240 mg and Relatlimab 80 mg, which blocks the PD-1 and LAG-3 pathways. This single-arm study is conducted in one center and includes only patients with resectable tumors. Treatment is given before surgical removal of the tumor, aiming to improve the chance of complete pathological response. During the study, patients will undergo assessments including tumor biopsies, imaging scans for measurable disease, and blood tests to check organ function and monitor safety. Researchers will track the pathological complete response rate at week 6 after treatment. Participants will be closely followed for recurrence-free survival and overall health. The study requires regular visits for evaluations to collect data on treatment effects and safety throughout the trial.

Researchers are evaluating neoadjuvant dual immunotherapy targeting PD-1 and LAG-3 pathways in patients with resectable stage I to III Merkel cell carcinoma. This phase 2, open-label, single-center clinical trial aims to improve recurrence-free survival and achieve a higher pathological complete response rate compared to previous nivolumab monotherapy studies. Participants receive a fixed dose combination of Nivolumab 240 mg and Relatlimab 80 mg before surgery. The treatment focuses on inhibiting two immune checkpoint pathways to enhance immune response against the cancer. The study involves a single treatment group without a control arm, and patients will be closely monitored during and after the neoadjuvant therapy period. During the study, patients undergo assessments including tumor measurement by RECIST 1.1 criteria, blood tests to evaluate organ function, and tissue sampling from tumors. Safety and treatment responses are monitored, with the main outcome measure being pathological complete response rate at week 6. Female participants must use effective contraception during treatment and for five months after the last dose. The study requires ongoing follow-up to assess recurrence-free survival and overall health status.

Researchers are conducting a Phase 1/2, open-label, multi-center study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and early antitumor activity of STX-001 administered by intratumoral injection in patients with advanced solid tumors. This first-in-human study includes patients receiving STX-001 alone or combined with pembrolizumab. The study features distinct cohorts including monotherapy targeting visceral lesions and a Phase 2 monotherapy cohort for advanced melanoma, aiming to explore treatment effects in multiple cancer types including triple-negative breast cancer and melanoma. The study involves multiple dose escalation cohorts for STX-001 given alone or combined with pembrolizumab, a PD-1 blocking antibody. STX-001, a self-replicating RNA therapy encoding IL-12 and delivered via lipid nanoparticles, is injected directly into tumor lesions, sometimes in multiple tumor sites. Phase 1 includes four monotherapy and four combination therapy cohorts plus an additional monotherapy cohort for visceral lesions. Phase 2 expands the study to evaluate STX-001 with pembrolizumab at the recommended dose, including cohorts for triple-negative breast cancer and advanced melanoma. Participants will undergo safety and tolerability assessments including monitoring dose-limiting toxicities, treatment-emergent and serious adverse events from consent until 30 days after the last dose. Clinical laboratory tests and vital signs will be regularly checked. Tumor biopsies before and after STX-001 injection will be performed when safe. The study also monitors pharmacokinetics and pharmacodynamics to understand drug behavior and immune effects. Total participation duration varies by cohort and treatment schedule.