Melanoma

Researchers are evaluating 177Lu-RAD204, a radiolabeled antibody targeting PD-L1, in a Phase 01 study involving participants with advanced solid tumors that express PD-L1. The study aims to assess the safety, tolerability, biodistribution, radiation dosimetry, and preliminary anti-tumor effects of this treatment. The main goal is to find the maximum tolerated dose and recommended doses for future studies in participants with cancers such as NSCLC, SCLC, triple-negative breast cancer, melanoma, head and neck cancer, endometrial cancer, and others with specific genetic markers. The study includes a pre-screening period for PD-L1 testing if needed, followed by a screening period lasting up to four weeks. Participants undergo a Phase 0 Imaging Period where a low dose of 177Lu-RAD204 is given to assess imaging quality, safety, and dosimetry over two weeks. This may be followed by a Phase 1 Treatment Period with escalating doses of 177Lu-RAD204 administered in cycles lasting six weeks each. Participants may receive multiple treatment cycles based on clinical benefit and safety evaluations. Dose-limiting toxicity is monitored for six weeks after the first treatment dose, and dosing intervals may be adjusted as agreed by the study team. During the study, participants will have imaging scans, safety evaluations, and laboratory tests to track the distribution and effects of 177Lu-RAD204. Researchers will measure pharmacokinetics, radiation dosimetry, and tumor responses up to 30 weeks. Safety and tolerability are closely monitored throughout. Participants must meet specific health and tumor criteria to join and will be observed for any adverse reactions. The total duration of participation varies depending on treatment response and tolerability.

Researchers are evaluating the use of the tracer 68GaGa-FAPI-46 in PETCT imaging to better assess how patients with advanced stage malignant melanoma respond to immune checkpoint inhibitor therapy ICT. The studys main goal is to determine if this new imaging method can improve response evaluation compared to the standard 18FFDG PETCT and possibly act as a biomarker for treatment effectiveness. Participants with advanced malignant melanoma will undergo two PETCT scans using the experimental tracer 68GaGa-FAPI-46 one before starting ICT treatment and another after three months. These scans are additional to their standard imaging. Blood samples will also be collected twice, and patients will receive standard ICT treatment as prescribed by their medical team. During the study, participants will have their scans and blood samples analyzed to observe changes in tracer uptake in both cancerous lesions and healthy tissues. Researchers will follow up passively for six months after the last PETCT scan to monitor outcomes. The primary outcome measured is the change in 68GaGa-FAPI-46 uptake in malignant lesions over a three-month period, with further monitoring extending to nine months total from enrollment.

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 12 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 MDNA11s effects alone and with pembrolizumab.

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 studying the safety and initial effects of T3011, given directly into tumors, alone and combined with the intravenous drug pembrolizumab. This Phase 12a open-label study focuses on adults with advanced or metastatic solid tumors, including melanoma, head and neck squamous cell carcinoma HNSCC, sarcoma, cutaneous squamous cell carcinoma cSCC, and non-small cell lung cancer NSCLC. The study aims to find safe dose levels and assess how well these treatments are tolerated and work in these cancer types. The study involves several groups Phase 1 tests increasing doses of T3011 alone to determine a recommended dose. Phase 2a Part 1 evaluates T3011 alone in participants with melanoma, HNSCC, sarcoma, and cSCC. Phase 2a Part 2 studies T3011 with pembrolizumab in NSCLC patients. A rollover arm allows participants whose cancer progresses on T3011 alone to receive the combination treatment. T3011 is given as an intratumoral injection every two weeks, and pembrolizumab is given intravenously every three weeks when combined. Participants will have tumor biopsies, imaging, and laboratory tests to monitor safety, drug levels, and cancer response. Researchers will track side effects and measure outcomes like tumor response and survival for up to two years after the first dose. Safety and tolerability are closely followed throughout, with additional monitoring for immune responses and drug presence in bodily fluids. Participants may be followed for up to one year after their last treatment dose to assess overall survival and long-term effects.

Researchers are evaluating the safety, tolerability, antitumor activity, and immune response of LM103 Injection in patients with advanced solid tumors, including melanoma, non-small cell lung cancer, and cervical cancer. This open-label, single-arm exploratory study aims to assess how well this treatment works and how safe it is for patients whose existing treatments are ineffective or unavailable. The treatment involves harvesting tumor-infiltrating lymphocytes TILs from the patients tumor sample, expanding them ex vivo, and then transferring them back to the patient intravenously after chemotherapy with cyclophosphamide and fludarabine. LM103 Injection is given as a single dose on day 1, combined with interleukin-2 IL-2 therapy to support immune response. The study plans to enroll between 9 and 15 patients. Participants will undergo laboratory tests, imaging, and physical assessments to monitor response and safety for up to two years. Researchers will track adverse events for one year and evaluate tumor response, disease control, progression-free survival, and changes in immune activity. The total study duration includes treatment, follow-up, and monitoring to better understand the effects of LM103 Injection in advanced solid tumors.

Researchers are evaluating the tolerability, safety, and early effectiveness of T3011 in adults with advanced melanoma. This clinical study is designed as a phase IbIIa trial to understand how participants with measurable melanoma lesions respond to this treatment. The study is led by Shanghai Pharmaceuticals Holding Co., Ltd and focuses on treatment outcomes over approximately two years. Participants receive T3011 delivered directly into the tumor every two weeks. This treatment period is followed by ongoing monitoring to assess responses and any side effects. The trial includes a single group of participants all receiving T3011, without a comparison placebo or alternative treatment group. Throughout the study, participants undergo various assessments including laboratory tests and evaluations of tumor response. Researchers measure treatment-emergent adverse events and objective response rate as primary outcomes, along with disease control rate, remission duration, progression-free survival, and overall survival as secondary outcomes. The total study duration is approximately two years, during which safety and efficacy are closely monitored.

Researchers are investigating metastatic colorectal cancer mCRC patients who have a specific genetic change called the BRAFV600E mutation. This rare subtype of mCRC often shows poor response to current treatments and has a generally poor outlook. The study aims to collect detailed clinical data and biological samples to better understand this condition, including how patients respond to treatments and what factors predict their survival. It focuses on real-world treatment outcomes and biological markers that might influence therapy choices and resistance. Participants will provide blood samples at multiple times during their treatment, including before and during the first three treatment cycles, at 3 and 6 months after starting each treatment line, and when disease progression occurs following certain therapies. The study gathers up to 390 mL of blood per participant over time to analyze circulating tumor DNA and immune environment factors. This observational approach will help researchers identify biomarkers related to treatment response and disease progression. During the study, participants clinical progress and survival will be tracked for up to five years. Researchers will review overall survival from diagnosis to death and assess how prognostic markers relate to progression-free survival and response to treatments. The study involves collecting tumor tissue samples and blood tests, along with routine follow-up visits. All data collected will contribute to understanding BRAFV600E mCRC and improving future treatment strategies.

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 the safety and feasibility of giving the Tetanus Diptheria Td vaccine or the Polio Boost Immunization IPOL to patients with advanced metastatic melanoma who are receiving immune checkpoint inhibitor IO therapy as part of their standard care. The study aims to see if these vaccines can be safely administered during the fourth cycle of IO therapy and to understand how the immune system responds. This is a Phase 1 treatment study conducted by Duke University. Participants receive either the Td vaccine or the IPOL vaccine at cycle 4 of their IO therapy. The first 15 subjects will get the Td vaccine as a 0.5 mL injection in the muscle near the largest tumor, either in the thigh or upper arm. Subjects 16 through 25 will receive the IPOL vaccine, also as a 0.5 mL injection given intramuscularly or subcutaneously near the largest tumor. Blood and tissue samples are collected before starting IO therapy, at cycle 4 before vaccination, and again 12 to 17 days after the vaccine. Participants are involved in regular assessments including research blood draws and tissue biopsies to evaluate safety and immune response. The main outcomes measured include the number of subjects who successfully receive the vaccine after 4 cycles of IO therapy and any changes in adverse events related to the vaccine or study procedures. Safety is monitored through scans and lab tests up to 8 to 12 weeks post-vaccine. Preliminary efficacy is also explored over a period of up to 36 months. The overall study duration may last several months from consent through post-vaccine follow-up.