Buderim

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 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 conducting a Phase III, randomized, open-label multicenter study to evaluate the effectiveness and safety of giredestrant compared with fulvestrant. Both drugs are combined with the investigators choice of a CDK46 inhibitor palbociclib, ribociclib, or abemaciclib in participants with estrogen receptor-positive ER, HER2-negative advanced breast cancer who have become resistant to prior adjuvant endocrine therapy. Participants will be randomly assigned to one of two groups one group will receive giredestrant 30 mg orally daily on Days 1-28 of each 28-day cycle, while the other will receive fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1 and Day 1 of subsequent 28-day cycles. Both groups will also receive a CDK46 inhibitor chosen by the investigator, with dosing schedules depending on the specific inhibitor selected. Preperimenopausal women and men will receive a luteinizing hormone-releasing hormone LHRH agonist during treatment. Participants will be assessed for progression-free survival over up to 5 years, with additional measures including overall survival, response rates, duration of response, clinical benefit, and quality of life. Safety will be monitored through adverse event reporting, vital signs, and laboratory tests during treatment and up to 28 days after the last dose. The study is led by Hoffmann-La Roche and aims to provide detailed information on the treatments effects in this patient population.

This research aims to collect long-term safety and efficacy data for participants who have been using bomedemstat and are benefiting from it, or have achieved blood count remission in certain conditions. The study includes individuals with essential thrombocythemia ET, polycythemia vera PV, and myelofibrosis MF who have previously been in earlier bomedemstat trials. It does not involve hypothesis testing but focuses on extended monitoring. Participants will take oral bomedemstat capsules once daily for up to 10 years. The dose they start with will be the same as they used in their previous study before transitioning into this extension. This allows continuous assessment of the effects and safety of the medication over a long period. During the study, participants will be closely monitored for adverse events and any reasons for stopping treatment due to side effects. For those with ET or PV, the duration of their clinical response and remission will be tracked, as well as any progression to more severe conditions. Other outcomes include the frequency of blood clots and bleeding events. Participant involvement may last up to about 10 years, with regular assessments and safety checks throughout.

Researchers are evaluating treatments for people with advanced non-small cell lung cancer NSCLC that have specific genetic changes called HER2 mutations. This lung cancer has spread or cannot be controlled with current treatments. The study aims to compare how well a drug called sevabertinib works and how safe it is compared to standard treatment for this type of cancer. Participants will receive either sevabertinib tablets twice daily or standard treatment consisting of pembrolizumab combined with platinum-based chemotherapy given every 21 days by infusion. Those on standard treatment who experience disease progression may switch to sevabertinib. Treatment continues as long as participants benefit and do not have severe side effects or until they or their doctor decide to stop. During the study, participants will have imaging scans like CT, PET, MRI, and X-rays to monitor cancer spread. Doctors will also perform health checks including blood and urine tests, heart monitoring with ECG, pregnancy tests for women, and ask about symptoms or side effects. The main measure is progression-free survival assessed up to about 2 years, with additional outcomes related to survival, response rates, side effects, and quality of life followed up to 4 years.

Researchers are evaluating DCSZ11, a monoclonal antibody, as a treatment for patients with advanced or metastatic solid tumors. This Phase 1, multicenter, open-label study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and potential antitumor activity of DCSZ11 both alone and in combination with pembrolizumab. The study includes patients who have relapsed or refractory tumors and have limited or no effective standard therapy options. The study has two main phases Phase 1a Dose Escalation and Phase 1b Dose ExpansionOptimization. In Phase 1a, patients receive intravenous infusions of DCSZ11 every 3 weeks either as monotherapy or combined with pembrolizumab, with doses increased to find the maximum tolerated or planned dose. Phase 1b evaluates DCSZ11 combined with pembrolizumab or standard-of-care treatments like doxorubicin for soft tissue sarcoma and tebentafusp for uveal melanoma, using designs to optimize dosing and monitor safety continuously. Participants will undergo screening that includes biopsies, imaging, and laboratory tests to confirm eligibility and monitor response. Researchers will evaluate tumor response using established criteria such as RECIST and iRECIST over one year, and follow safety and survival outcomes for up to three years. The study involves regular clinic visits, safety assessments, and monitoring for immune responses and drug levels to understand treatment effects and tolerability.

Researchers are evaluating the role of sentinel node biopsy SNB compared to no retroperitoneal node dissection in women with early-stage endometrial cancer. This study aims to assess whether SNB causes any harm such as lymphoedema or morbidity, its cost-effectiveness, and if it affects disease-free survival. The trial is conducted in two stages Stage 1 with 444 patients focuses on recovery and quality of life, while Stage 2 with an additional 316 patients examines long-term disease outcomes. Participants will undergo either total laparoscopic or robotic hysterectomy with bilateral salpingo-oophorectomy TH BSO combined with SNB using injected tracer dyes, or TH BSO without retroperitoneal node dissection. Some patients under 45 years with specific tumor features may keep their ovaries. Surgery may include omentectomy in high-risk cases. The SNB procedure involves identifying the first lymph node that drains the tumor area using dye injections. During the study, participants will be monitored for recovery including adverse events, lymphoedema, quality of life, and healthcare costs over 12 months. Long-term follow-up will measure disease-free survival and overall survival up to 4.5 years after surgery. Evaluations will include clinical assessments, imaging, patient questionnaires, and molecular testing. The research team will also track surgery details, hospital stays, and the need for additional treatments throughout the study period.

Researchers are evaluating the safety and performance of the PRIMUS System, a device designed to provide neurostimulation to branches of the trigeminal and occipital nerves, for treating resistant migraine. The study focuses on patients with chronic or high-frequency episodic migraine who have not responded to multiple preventive drug therapies. It aims to assess clinical benefits and safety over a 12-week period. Participants will be randomly assigned in a double-blind manner to one of several groups including active therapy modalities or sham therapy. The PRIMUS System delivers subcutaneous neurostimulation, and the study compares different therapy approaches to evaluate their effects on migraine symptoms. The study is set to run from June 2024 to January 2029. During the study, participants will be monitored over 12 weeks to evaluate both safety and effectiveness. Researchers will assess clinical outcomes related to migraine treatment, with follow-ups as per study protocols. This period will involve treatment administration and regular evaluations to collect data on responses and any side effects experienced.