Buderim

Researchers are evaluating MDNA11, a long-acting "beta-only" recombinant interleukin-2 designed to activate immune cells that attack cancer while minimizing stimulation of cells that suppress immunity. This Phase 1/2 open-label study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of MDNA11 alone or combined with pembrolizumab in patients with advanced or metastatic solid tumors. The study includes dose-escalation and dose-expansion parts for both monotherapy and combination therapy with pembrolizumab. MDNA11 is given intravenously every two weeks with doses ranging from 0.003 to 0.6 mg/kg for monotherapy, while dose ranges for combination therapy are also evaluated. Treatment continues until progression, withdrawal, or loss to follow-up, with tumor assessments by CT or MRI every 8 weeks. Participants will undergo regular imaging scans every 8 weeks to monitor tumor response and safety assessments throughout the 24-month study. Researchers will track recommended doses for expansion, treatment-related adverse events, and overall safety. The study involves up to 115 patients across multiple sites and includes long-term monitoring for up to 24 months.

Researchers are evaluating intratumoral ONM-501 alone and in combination with cemiplimab, a PD-1 checkpoint inhibitor, in patients with advanced solid tumors and lymphomas. This phase 1, multicenter, open-label study aims to find the maximum tolerated dose, minimum effective dose, and recommended dose for expansion of ONM-501. The study includes patients whose tumors are advanced, nonresectable, or recurrent, and for whom no standard therapy is available. The trial has three parts: monotherapy dose escalation, combination therapy dose finding, and combination therapy dose expansion in specific tumor types. ONM-501 is given as intratumoral injections once weekly for three weeks followed by three weeks without treatment, in 21-day cycles. Cemiplimab is administered intravenously at 350 mg every three weeks during the combination phases. The dose escalation uses accelerated titration and a "Rolling 6" enrollment method to allow staggered patient entry. Participants will be closely monitored for treatment-emergent adverse events, dose-limiting toxicities, and serious adverse events for up to about 24 months. Assessments include physical exams, laboratory tests, and tumor measurements. The expansion phase will enroll patients into one to three indication-specific groups based on the recommended doses found. Safety and tolerability will be key outcomes throughout the study duration.

The primary purpose of the study is to transition participants into an extension study to collect long-term safety and efficacy data. The study will include participants who are safely tolerating bomedemstat, receiving clinical benefit from its use in estimation of the investigator, and have shown the following criteria: * Participants from the IMG-7289-202/MK-3543-005 (NCT05223920) study must have received at least 6 months of treatment with bomedemstat; * Essential thrombocythemia (ET) and polycythemia vera (PV) participants from studies other than IMG-7289-202/MK-3543-005 must have achieved confirmed hematologic remission. No hypothesis testing will be conducted in this study.

Researchers are investigating better treatments for people with advanced non-small cell lung cancer (NSCLC) that has specific genetic changes called HER2 mutations. Advanced NSCLC refers to lung cancers that have spread or are unlikely to be controlled with current treatments. HER2 is a protein that helps cells grow, and mutations cause abnormal HER2 leading to cancer growth. This Phase 3 study aims to compare the safety and effectiveness of a new drug, sevabertinib, against standard treatment in patients with this type of lung cancer. Participants will be randomly assigned to receive either sevabertinib tablets twice daily by mouth or standard treatment consisting of cycles of intravenous infusions including drugs like pembrolizumab, cisplatin, carboplatin, and pemetrexed every 21 days. Treatments continue as long as participants benefit without severe side effects or until they or their doctors decide to stop. Participants on standard treatment whose disease worsens may switch to sevabertinib and continue until progression, intolerable side effects, or decision to stop. During the study, participants will undergo imaging scans such as CT, PET, MRI, and X-rays to monitor cancer spread. Health checks include blood and urine tests, heart monitoring with ECG, and pregnancy tests for women. Researchers will ask about participants’ well-being and record any medical problems or side effects experienced. The main outcome measured is progression-free survival over up to about two years.

Researchers are evaluating DCSZ11 as a single treatment and in combination with pembrolizumab in patients with advanced or metastatic solid tumors. This multicenter, open-label Phase 1 study includes a Dose Escalation Phase (Phase 1a) and a Dose Expansion/Optimization Phase (Phase 1b). The goal is to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of DCSZ11, including combinations with other therapies in certain relapsed or refractory solid tumors. DCSZ11 is given as an intravenous infusion every 3 weeks during the study. Phase 1a involves dose escalation of DCSZ11 alone and with pembrolizumab, increasing doses up to a maximum planned level. Phase 1b includes a dose expansion and optimization stage using a Simon two-stage design for certain cancer types. There is also a safety lead-in and expansion for DCSZ11 combined with standard-of-care treatments like doxorubicin for soft tissue sarcoma or tebentafusp for uveal melanoma. Participants will undergo evaluations including biopsies, imaging scans, and laboratory tests to monitor tumor response and safety. Researchers will track treatment emergent adverse events, dose-limiting toxicities, and overall response rates over periods ranging from 21 days to up to 3 years. Patients will be monitored closely during treatment cycles, and safety follow-up will be conducted to assess long-term effects and treatment tolerability.

Endometrial cancer is the most common gynecological cancer, and this trial focuses on early-stage disease confined to the uterus. Researchers are evaluating the value of sentinel node biopsy (SNB) compared to no retroperitoneal lymph node dissection in treatment. The study aims to determine if SNB affects patient outcomes, costs, and potential harms such as lymphedema, while also assessing disease-free survival over time. This is a Phase III randomized clinical trial designed to clarify these important questions. Participants will be randomly assigned to one of two groups: one receiving hysterectomy and removal of fallopian tubes and ovaries with SNB, and the other receiving the same surgery without retroperitoneal node dissection. The SNB procedure involves injecting a tracer dye near the tumor to identify the first lymph node(s) that drain the area, which are then surgically removed. For some younger women with less invasive cancer, ovary removal may be omitted. Treatment details, including surgery and biopsy procedures, will be carefully followed. Throughout the study, participants will be monitored for recovery and side effects such as lymphoedema, quality of life, and adverse events. Researchers will use clinical exams, imaging, and pathology to check for disease recurrence up to 4.5 years after surgery. Other assessments include cost-effectiveness, patient-reported outcomes, and survival. The primary outcomes are the time to return to usual activities at 12 months and disease-free survival at 4.5 years. Safety and health will be closely tracked, with a total follow-up period extending beyond four years.

Researchers are evaluating the safety and performance of the PRIMUS System, a device designed to provide subcutaneous neurostimulation to the branches of the trigeminal and occipital nerves, for treating resistant migraine. This study focuses on adults diagnosed with chronic or high-frequency episodic migraine who have not responded to multiple preventive medications. The goal is to assess both clinical benefit and safety over a 12-week period. Participants receive treatment using the Salvia PRIMUS System, which delivers neurostimulation to specific nerve branches associated with migraine. The study is randomized, double-blind, and controlled, ensuring a careful comparison of outcomes. The investigational device is applied with attention to device safety and effectiveness. During the study, participants are monitored for safety and effectiveness over 12 weeks. Assessments include clinical evaluations to track migraine symptoms and any potential side effects. Throughout the trial, researchers collect data on treatment performance, patient response, and overall well-being to understand the device's impact on resistant migraine.