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Researchers are studying whether combining calderasib, a targeted therapy for the KRAS G12C mutation, with subcutaneous pembrolizumab can treat non-small cell lung cancer (NSCLC). The study aims to determine if people receiving calderasib with pembrolizumab live longer without their cancer growing or spreading compared to those receiving pembrolizumab with chemotherapy. This is a phase 3, randomized, open-label, multicenter clinical trial focusing on participants with advanced or metastatic nonsquamous NSCLC carrying the KRAS G12C mutation. Participants will receive one of two treatment combinations. One group will take calderasib orally along with subcutaneous pembrolizumab and berahyaluronidase alfa injections. The other group will receive subcutaneous pembrolizumab combined with chemotherapy drugs pemetrexed and a platinum-based drug, either carboplatin or cisplatin, administered by intravenous infusion. These treatments are given as first-line therapy, and the study evaluates their safety and effectiveness. During the study, researchers will monitor participants for progression-free survival, especially focusing on those with at least 1% PD-L1 tumor proportion score, for up to approximately 48 months. Participants will undergo regular assessments to track cancer progression and response to treatment. Safety and efficacy data will be collected throughout the study to understand how well the treatments work and their side effects over time.

Researchers are investigating sacituzumab tirumotecan (MK-2870) alone or combined with other treatments to treat certain gastrointestinal cancers. These include colorectal cancer that cannot be removed by surgery or has spread, advanced pancreatic ductal adenocarcinoma, and biliary tract cancer. The study aims to understand the safety and tolerability of sacituzumab tirumotecan and measure how many participants respond to the treatment by having their cancer shrink or disappear. Participants may receive sacituzumab tirumotecan by intravenous infusion alone or with other anticancer drugs such as fluorouracil (5-FU), leucovorin or levoleucovorin, cisplatin, and pembrolizumab. Rescue medications like diphenhydramine, H2 receptor antagonists, acetaminophen, dexamethasone, and a steroid mouthwash are given to prevent infusion reactions and oral side effects. Supportive care treatments for side effects, including antidiarrheal and antiemetic agents, are allowed throughout the study. During the study, researchers monitor participants for dose-limiting toxicities within about 4 weeks and track adverse events, treatment discontinuations, and tumor response over up to approximately 63 months. Assessments include safety evaluations and measuring cancer response using standardized criteria. This long-term follow-up helps evaluate both the effectiveness and safety of the treatments being studied.

Researchers are evaluating the effects of oral neflamapimod, a specific inhibitor of the enzyme p38 alpha kinase, on recovery after moderate to severe acute ischemic stroke. The study aims to determine whether neflamapimod can improve residual physical disability and cognitive dysfunction following such strokes. This is a Phase 2, double-blind, placebo-controlled clinical trial targeting adults who have recently experienced an ischemic stroke in the brain's anterior circulation. Participants will receive either neflamapimod capsules containing 40 mg of the active drug or placebo capsules that look identical but contain no active ingredients. The treatment will be administered over a 12-week period. The study compares motor recovery and other functional outcomes between the neflamapimod and placebo groups to assess the investigational drug's impact. During the study, participants will undergo various assessments including the Fugl-Meyer Assessment of Motor Recovery, the Timed Up and Go Test, and the National Institutes of Health Stroke Scale motor score. These evaluations will measure changes from baseline to Week 12 to track motor and cognitive recovery. Safety monitoring and adherence will be conducted through regular evaluations. The total participation period covers enrollment through the end of treatment at 12 weeks.

Researchers are investigating new treatments for advanced ovarian cancer, specifically in patients who do not have homologous recombination deficiency (non-HRD positive). This Phase 3 study aims to assess whether maintenance treatment with sacituzumab tirumotecan (sac-TMT), alone or combined with bevacizumab, can improve progression-free survival compared to the current standard care after initial platinum-based chemotherapy and surgery. Participants receive sacituzumab tirumotecan through intravenous infusion at a dose of 4 mg/kg. Some also receive bevacizumab intravenously at 15 mg/kg as part of their maintenance treatment. Before sac-TMT infusion, participants are given prophylactic steroid mouthwash and recommended rescue medications including histamine-1 and histamine-2 receptor antagonists, acetaminophen or equivalent, and dexamethasone or equivalent. The study compares these treatments to standard care or observation following first-line chemotherapy. During the study, participants are monitored for progression-free survival for up to approximately 49 months. Researchers will assess how long participants live without their cancer getting worse. Throughout the trial, safety and response to treatment are evaluated. The study includes women aged 18 years and older who have completed surgery and first-line chemotherapy with specific responses and meet certain health criteria.

Researchers are evaluating the safety of aerosolized RSP-1502 in people with cystic fibrosis who have chronic lung infections caused by Pseudomonas aeruginosa. This phase 1b/2a study compares different doses of RSP-1502 to an active control, aiming to find the maximum tolerated dose (MTD) and assess safety outcomes. Participants must meet specific lung function and infection criteria to join the study. The study involves administering RSP-1502 or an active control solution by inhalation using a nebulizer for 14 days. RSP-1502 contains tobramycin and CaEDTA in a sterile solution, while the active control is a tobramycin inhalation solution. After dose escalation to identify the MTD, a dose expansion phase compares the MTD of RSP-1502 to the active control for another 14 days. Participants will then be followed for 14 days after treatment ends. Participants will have their lung function tested with spirometry and undergo electrocardiograms on specific days during treatment. Researchers will monitor for any treatment-related adverse events and serious adverse events throughout the 28-day treatment and follow-up period. They will also track pulmonary exacerbations and other safety measures. The total participation includes dosing and a 14-day follow-up after treatment completion.

Researchers are investigating new treatments for children and young people with relapsed or refractory B-cell non-Hodgkin Lymphoma (B-NHL), a type of cancer affecting lymph nodes and organs like the liver or spleen. Current treatments have limited success and many side effects, curing only about 30% of patients. This global trial aims to find better and safer medicines by testing novel agents in this rare cancer setting, using an adaptive trial design that allows continuous evaluation and adjustment. The trial has three treatment groups, each testing a different new medicine: bispecific antibodies (BsAbs), antibody-drug conjugates (ADC) combined with standard chemotherapy, and chimeric antigen receptor (CAR) T-cells. Patients may be assigned to any available group they qualify for, and if a treatment does not work, they might switch to another group. The trial uses a Bayesian adaptive design to efficiently decide whether a treatment is effective and can stop ineffective treatments early to introduce new ones. Participants will receive the assigned treatments and be monitored closely through scans, biopsies, and laboratory tests to evaluate disease response and safety. The main outcomes include measuring objective responses and complete remissions at specified time points. Children and young people will be followed for at least two years after treatment to monitor for side effects and long-term health. The study includes comprehensive assessments and is conducted across multiple international centers.

Researchers are evaluating whether the drugs retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in adults with metabolic dysfunction-associated steatotic liver disease (MASLD) who are at high risk. This Phase 3 trial enrolls about 4,500 adults with MASLD identified by non-invasive tests indicating an increased likelihood of developing serious liver problems. The study aims to understand how these treatments might affect liver health over time compared to a placebo. Participants will be randomly assigned to receive either retatrutide, tirzepatide, or a placebo, all given by subcutaneous injection. The study will last approximately 224 weeks, during which participants may attend 25 to 30 clinic visits for monitoring and assessment. After the main study, eligible participants can join an optional 2-year extension where all will receive either retatrutide or tirzepatide regardless of their original group. Throughout the trial, participants’ liver function and disease progression will be closely monitored through various health assessments. Researchers will track the time to the first major adverse liver event as the main outcome. Safety and health status will be evaluated regularly during clinic visits, ensuring thorough observation over the long study period.

Researchers are conducting a Phase 1 study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of a humanized monoclonal antibody called CLYM116 in healthy adult volunteers aged 18 to 60 years. CLYM116 selectively binds to a proliferation inducing ligand (APRIL). This randomized, double-blind, placebo-controlled study will include up to 48 participants in up to five groups to evaluate the effects of this investigational drug. Participants will receive either CLYM116 or a placebo through subcutaneous injections. The study includes single-ascending-dose and multiple-ascending-dose phases to monitor the body's response to different doses. The placebo group will receive injections matching the volume of the active drug. The study is conducted at a single center with careful dosing schedules and monitoring. During the study, participants will undergo medical exams, ECGs, laboratory tests, and monitoring for any adverse events, including injection site reactions. Safety and tolerability will be tracked from screening through day 85 or the final follow-up visit. The study also evaluates pharmacokinetics, pharmacodynamics, and immunogenicity. Participants' adherence and health status will be closely observed throughout the study period.

Researchers are evaluating a new treatment called HB2198, a tetravalent bispecific antibody targeting CD19 and CD20, in adults with moderately to severely active systemic lupus erythematosus (SLE), including lupus nephritis and extra-renal lupus. This Phase 1, open-label, dose escalation study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early clinical effects of HB2198. Approximately 30 participants will receive treatment and be followed for one year to monitor disease activity, immune response, and kidney health. Participants will receive two intravenous doses of HB2198 on Day 1 and Day 8 following a modified 3+3 dose escalation design. The study evaluates dose limiting toxicities and pharmacodynamics to identify the recommended dose for further study. HB2198 is designed to enhance B-cell depletion through dual targeting of CD19 and CD20 and optimized immune system engagement. The total participation duration is about 13 months, including follow-up. During the study, participants will have regular safety assessments, including monitoring for side effects and serious adverse events on Days 1, 8, 14, and 29. Disease activity will be measured using several assessment tools, such as SLEDAI 2K, physician global assessment, and quality of life questionnaires. Laboratory tests and kidney function will be closely monitored. Researchers will also track immune biomarkers and response to treatment throughout the study period to understand HB2198’s effects.

Researchers are evaluating the safety and tolerability of DB-1311/BNT324 in adults with advanced or metastatic solid tumors in this Phase 1/2a trial. The study includes a dose-escalation phase to find the maximum tolerated dose and recommended Phase 2 dose, followed by a dose-expansion phase to confirm safety and explore effectiveness, including in prostate cancer patients receiving novel hormone therapy. Additionally, a sub-study will assess the effects of other drugs on DB-1311's behavior in the body. During Phase 1, participants receive increasing doses of DB-1311 administered intravenously using an accelerated titration and classic 3+3 design to determine safe dosage levels. Phase 2a expands on this to further evaluate safety and tolerability, with DB-1311 given alone or combined with hormone therapy drugs such as enzalutamide or abiraterone for prostate cancer. The study also investigates drug interactions with lopinavir/ritonavir and itraconazole. Treatment schedules and dosing details follow the study protocol at multiple centers. Participants will undergo various assessments including safety labs, vital signs, electrocardiograms, heart function tests, and performance status evaluations up to approximately one year after treatment. Researchers will monitor treatment-related toxicities, serious adverse events, and response rates. The involvement includes tumor biopsies for biomarker analysis and adherence to follow-up visits. The total study duration varies by phase, with ongoing safety and efficacy monitoring throughout.