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 1/2a 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 PET/CT 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, PET/CT imaging will be performed to capture detailed images of the tumors. Within one week, participants will also undergo a whole-body PET/CT 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 PET/CT 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 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 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 3+3 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 3+3, 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 therapy’s effects and safety profile.

Researchers are evaluating new treatment options for people with high-risk non-muscle invasive bladder cancer (HR NMIBC), a type of bladder cancer that affects the inner lining of the bladder but has not spread to the muscle or beyond. This includes carcinoma in situ (CIS), a flat form of bladder cancer limited to the bladder's surface. The study aims to find out if adding intismeran autogene, an immune system-targeting treatment, to the standard Bacillus Calmette-Guerin (BCG) therapy can improve outcomes for people with HR NMIBC by helping the immune system attack the cancer more effectively. Participants are assigned to different groups. One group receives both intismeran autogene by intramuscular injection every three weeks for nine doses along with BCG treatment given once weekly for six weeks, followed by additional weekly doses at later weeks. Another group receives BCG alone on the same schedule, while a third group receives only intismeran autogene. The study compares these treatments to see if the combination improves survival without cancer growth, spread, or return. During the study, participants will be monitored for up to approximately five years to track event-free survival, recurrence-free survival, overall survival, and other outcomes. Researchers will also evaluate adverse events and treatment tolerability. Follow-up includes assessments at regular intervals to observe disease status and safety. The total participation time may last several years to gather long-term data on treatment 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 investigating new treatment options for metastatic cervical cancer, a type of cancer that starts in the cervix and has spread to other parts of the body. This study focuses on evaluating sacituzumab tirumotecan (sac-TMT), an antibody drug conjugate designed to target cancer cells, in combination with pembrolizumab and bevacizumab. The main goals are to assess the safety and tolerability of these drugs given together and to see if they help patients live longer or delay cancer progression compared to standard treatments. The study has two parts. In Part 1, participants receive sac-TMT, pembrolizumab, and bevacizumab to assess safety. In Part 2, all participants first receive standard induction treatment with pembrolizumab, paclitaxel, and cisplatin or carboplatin, with optional bevacizumab. Those whose cancer does not worsen then start maintenance treatment, where they are randomly assigned to receive either pembrolizumab alone or sac-TMT plus pembrolizumab. Bevacizumab may also be added during maintenance at the doctor's discretion. Treatments are given through intravenous infusions on schedules that range from every 2 to 6 weeks, lasting up to approximately 20 months. During the study, participants will have regular evaluations to monitor safety and how well the treatments work. Assessments include tracking side effects, cancer progression using imaging criteria, overall survival, and quality of life questionnaires focused on health status and physical function. The research team will observe participants for several years to collect data on treatment outcomes and tolerability, with some follow-up lasting up to about 69 months.

Researchers are evaluating the PVX7 immunotherapy vaccine in adult women with advanced cervical cancer who have completed their primary treatment, such as surgery, radiation, or chemotherapy. This Phase 1 clinical trial focuses on the safety and immune response of PVX7, studying how well it is tolerated and whether it stimulates the immune system. The study is sponsored by the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Participants are randomly assigned to one of two groups. One group receives the pBI-11 DNA vaccine by intramuscular injection and then TA-HPV vaccine through skin inoculation. The other group receives both pBI-11 DNA and TA-HPV vaccines via intramuscular injection. Vaccinations occur at weeks 1, 5, and 9. The trial includes a two-year follow-up period according to standard care practices. During the study, participants will undergo safety assessments to monitor for adverse events and immune response tests for up to 12 months. Researchers will track presence of HPV DNA and immune cell activity. Participants must follow specific care instructions after vaccination and avoid close contact with certain vulnerable individuals for one month. The total participation includes treatment and follow-up visits over two years to evaluate safety, feasibility, and immune effects of the PVX7 vaccine.