Cervical Dysplasia / Intraepithelial Neoplasia (CIN)

Researchers are evaluating 177Lu-BetaBart, a 177Lu-labeled anti-B7-H3 monoclonal antibody, in patients with various relapsed or refractory solid tumors that are locally advanced, inoperable, or metastatic. This Phase 12a study aims to understand the safety, tolerability, how the drug moves through and affects the body, and early signs of anti-tumor activity. Eligible participants include adults 18 and older with cancers such as castration-resistant prostate cancer, colorectal cancer, lung cancers, head and neck cancer, ovarian, cervical, endometrial, triple negative breast cancer, and esophageal squamous cell carcinoma who have shown disease progression after recent treatments. The study has two main parts a Phase 1 dose escalation phase to find the maximum tolerated or recommended dose using a Bayesian design, and a Phase 2a dose expansion phase at that recommended dose to confirm safety and observe preliminary anti-tumor effects. Participants receive 177Lu-BetaBart through intravenous infusions every six weeks. Each phase includes a screening period, treatment and imaging period, and a safety and long-term follow-up period to closely monitor outcomes and side effects. During the study, participants undergo assessments including imaging for disease evaluation, laboratory tests for organ function and drug effects, and monitoring of side effects for up to 30 weeks. Key outcomes include determining the suitable dose for future studies, tracking adverse events, and measuring anti-tumor activity through objective response rates and biochemical responses in prostate cancer. Pharmacokinetics, radiation dosimetry, and biokinetics of the drug are also measured at specified time points. Safety and tolerability are evaluated continuously, with follow-up to monitor long-term effects and overall health.

Researchers are evaluating the diagnostic value of a new protein-specific probe called 18F-T2 in PETCT imaging for people with solid tumors that are likely to express high levels of CAIX protein. The study will also assess how safe and tolerable the 18F-T2 injection is, as well as measure its radiation dosage. This research is important to better understand how well 18F-T2 can detect these tumors compared to standard imaging techniques. Participants with tumors suspected to express high levels of CAIX will receive an intravenous injection of 18F-T2. About an hour after the injection, PETCT imaging will be performed to capture detailed images of the tumors. Within one week, participants will also undergo a whole-body PETCT scan using 18F-FDG, a commonly used imaging agent, to allow comparison between the two imaging methods. During the study, participants will be monitored for any adverse events within 24 hours after the 18F-T2 injection to evaluate safety and tolerability. Researchers will measure the diagnostic sensitivity and specificity of 18F-T2 PETCT for detecting CAIX-positive tumors. They will also assess uptake values in tumors on both 18F-T2 and 18F-FDG scans, analyze the correlation between 18F-T2 uptake and CAIX expression in tissue samples, and evaluate radiation dosimetry. The study will continue until one month after completion for outcome assessments.

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 evaluating the safety and effectiveness of CD70-targeted CAR-T cells in treating patients with CD70-positive advanced or metastatic gynecologic cancers. This Phase 1 study focuses on patients who have not responded to standard treatments and aims to find the best doses and infusion methods for these CAR-T cell therapies. The study has two groups based on how the CAR-T cells are given one group receives the treatment through intravenous infusion, and the other through intraperitoneal injection. Each group undergoes two phases a dose discovery phase that uses a dose-escalating design to find recommended doses, followed by a dose expansion phase to further evaluate safety and effectiveness at those doses. Participants receive doses ranging from 1 to 10 million cells per kilogram. Participants will be closely monitored for adverse events and treatment effects over time. Researchers will assess safety outcomes within the first 28 days after infusion and effectiveness outcomes such as disease control and response rates over three months, with longer-term follow-up up to two years. Various lab tests, imaging scans, and clinical evaluations will be done to track how the CAR-T cells behave and impact the cancer. The total study duration and detailed monitoring are designed to ensure participant safety and collect data on how well the CAR-T cells work.

Researchers are evaluating the safety and effectiveness of CD70-targeted CAR-T cells in treating patients with CD70-positive advanced or metastatic solid tumors. This phase 1, single-center study involves two groups based on the delivery method intravenous infusion and intraperitoneal injection. The study aims to find the recommended doses and infusion patterns for these treatments using a dose-escalation design. Each group undergoes two phases a dose discovery phase with four dose levels using a 33 design to recruit about 12 subjects, followed by a dose expansion phase where one or two dose levels are further tested for safety and efficacy with about 6 subjects per dose group. Before CAR-T cell infusion, patients receive lymphodepletion with fludarabine and cyclophosphamide. The doses range from 1 to 10 million cells per kilogram. During the study, participants will be closely monitored for side effects and treatment responses. Researchers will measure adverse events within 28 days and determine the maximum tolerated dose. Effectiveness outcomes include disease control rate, objective response rate, duration of response, progression-free survival, and overall survival over periods up to two years. The study also evaluates the behavior of CAR-T cells in the body over three months. Participants organ functions, quality of life, and safety will be regularly assessed throughout the trial.

Researchers are evaluating the safety and tolerability of a new CAR-T cell therapy targeting CD70 in patients with advanced or metastatic solid tumors that express CD70. This phase I study aims to find the highest dose patients can safely receive and to recommend a dose for future studies. The trial focuses on patients who have not responded to or cannot tolerate standard treatments and have measurable tumors. The study has two groups receiving CD70-targeted CAR-T cells either by intravenous infusion or intraperitoneal injection. Each group includes three dose levels using a dose-escalation design called 33, with about nine patients planned for each group. Before receiving the CAR-T cells, patients are treated with Fludarabine and Cyclophosphamide. This is an open-label trial without randomization or masking. Participants will be closely monitored for adverse events and dose tolerance during the first 28 days after infusion. Researchers will also assess disease control, objective response rates, treatment duration, and pharmacodynamics over three months. Evaluations include imaging scans, blood tests, and clinical assessments. The total study duration includes safety monitoring, with ongoing follow-up to understand the therapys effects and safety profile.

Researchers are studying new treatment options for people with high-risk non-muscle invasive bladder cancer HR NMIBC, including cases with carcinoma in situ CIS. HR NMIBC affects the lining of the bladder but has not spread to muscle or beyond. The study aims to learn if adding intismeran autogene V940 to the standard Bacillus Calmette-Guerin BCG immunotherapy can improve outcomes by helping the immune system attack the cancer more effectively. Participants are divided into groups receiving different treatments. One group Cohort A receives both intismeran autogene via intramuscular injection every 3 weeks for 9 doses and BCG instillations weekly in specific weeks over about 75 weeks. Another group receives only BCG following the same weekly schedule. A third group Cohort B receives intismeran autogene alone every 3 weeks for 9 doses. The study evaluates these treatments over several years. During the study, participants will have regular treatments and follow-up visits where researchers will monitor cancer progression, recurrence, and survival for up to approximately 5 years. Assessments include event-free survival, recurrence-free survival, overall survival, response rates, time to cystectomy, and safety outcomes such as adverse events and treatment discontinuation. The study is randomized and open-label, with detailed long-term monitoring planned.

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 investigating new treatments for metastatic cervical cancer, which is cancer that has spread beyond the cervix, the lower part of the uterus. This study evaluates the safety and effectiveness of the antibody drug conjugate sacituzumab tirumotecan sac-TMT combined with pembrolizumab and bevacizumab. The goal is to find out if these treatments, given together or with some variations, help patients live longer or delay cancer progression compared to standard care. The study has two parts. In Part 1, participants receive sac-TMT, pembrolizumab, and bevacizumab together to assess safety. In Part 2, all participants first get standard induction treatment with pembrolizumab, paclitaxel, and cisplatin or carboplatin, possibly with bevacizumab. Those whose cancer does not worsen then enter maintenance treatment, where they are randomly assigned to receive either pembrolizumab alone or sac-TMT plus pembrolizumab, with optional bevacizumab. Participants are involved for up to about 20 months during maintenance treatment after up to 4 months of induction. The study monitors safety by tracking side effects and treatment discontinuations. Effectiveness is measured by progression-free survival and overall survival up to several years. Quality of life and physical functioning are also assessed through questionnaires. Treatments and evaluations occur through regular intravenous infusions and periodic monitoring visits.

Researchers are evaluating the PVX7 immunotherapy vaccine in female patients with advanced cervical cancer who have completed their initial primary treatment. This phase 1 feasibility trial aims to study the safety and immune response triggered by the vaccine. Patients are randomized to receive the vaccine via two different methods to understand which administration route may be feasible and safe. Participants are randomly assigned in equal groups to receive PVX7 immunotherapy either by intramuscular injection or skin inoculation. The vaccination schedule includes doses at weeks 1, 5, and 9. One group receives pBI-11 DNA twice by intramuscular injection followed by a skin inoculation dose of TA-HPV, while the other group receives pBI-11 DNA twice followed by an intramuscular dose of TA-HPV. After vaccination, patients are followed for two years according to standard care protocols. During the trial, participants undergo regular safety monitoring to track adverse events and immune responses over 12 months. Researchers measure cellular immune response, overall immune response, and the presence of circulating HPV DNA. Participants need to comply with study procedures and avoid close contact with certain vulnerable individuals for one month after vaccination. The study is led by the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and aims to assess the feasibility and safety of this immunotherapy approach in advanced cervical cancer patients.