Murdoch

Researchers are investigating the safety, tolerability, distribution in the body, radiation dose, and early anti-tumor effects of 177Lu-RAD204, a radiolabeled antibody targeting PD-L1, in adults with certain advanced solid tumors that express PD-L1 or have specific genetic markers. This Phase 0/1, first-in-human study aims to find the recommended doses for future studies by evaluating both imaging and treatment doses in participants with cancers such as lung, breast, melanoma, head and neck, endometrial, and others with relevant mutations or markers. The study includes several periods: a screening period lasting up to 4 weeks, followed by a Phase 0 imaging period where a low dose of 177Lu-RAD204 is given to assess imaging quality, safety, and radiation exposure over about 2 weeks. After this, participants enter the Phase 1 treatment period involving dose escalation of the therapeutic 177Lu-RAD204 with cycles lasting 6 weeks. Participants may receive multiple cycles if they benefit clinically and have acceptable safety and organ radiation levels. Dose limiting toxicities are monitored for 6 weeks after the first treatment dose, with flexibility for altered schedules if needed. Throughout the study, participants undergo imaging scans, safety assessments, and dosimetry measurements to track how the drug moves and acts in the body. Researchers measure various outcomes including time activity curves, radiation dose, pharmacokinetics, and biokinetics over 72 hours, as well as safety and tolerability over 6 weeks. The study carefully monitors the recommended doses for future exploration, and participants may be followed for clinical benefit and adverse events during treatment cycles and follow-up periods.

Researchers are evaluating sotatercept as a potential treatment for pulmonary arterial hypertension (PAH), a condition where blood vessels in the lungs thicken and narrow, causing high blood pressure in the lungs and overworking the heart. PAH symptoms include difficulty breathing and reduced ability to be active. Current standard treatments address symptoms but do not stop disease progression. This Phase 3 study focuses on the long-term safety and tolerability of sotatercept when added to standard PAH therapy. Participants in this long-term follow-up study receive sotatercept through subcutaneous injections every three weeks. Only individuals who completed prior sotatercept PAH studies without early discontinuation may join. This study continues the observation and assessment of participants over an extended period to learn about the effects and safety of sotatercept combined with background PAH treatments. During the study, participants will be regularly monitored for adverse events, treatment discontinuations, and the presence of anti-drug antibodies for up to approximately 90 months. Laboratory tests will evaluate blood components such as platelets, hemoglobin, creatinine, bilirubin, and liver enzymes. Changes from baseline in body weight, blood pressure, and electrocardiogram readings will also be tracked. The study involves adherence to visit schedules and compliance with study procedures to ensure comprehensive long-term safety data collection.

Primary immune thrombocytopenia (ITP) is a condition in which the immune system mistakenly destroys platelets, the cells that help stop bleeding. This leads to a low platelet count, making it easier to bruise or bleed. The trial investigates the long-term safety, tolerability, and effectiveness of mezagitamab in adults with chronic primary ITP who have previously participated in certain mezagitamab studies. It also examines how the body processes mezagitamab over time. Participants who completed the previous mezagitamab studies TAK-079-3002 or TAK-079-1004 and meet specific criteria will receive mezagitamab as a subcutaneous injection during this continuation study. The study is open-label and multicenter, focusing on continued treatment based on protocol requirements. The medication is given under medical supervision, and participants return to the study clinic several times throughout the study. During their participation, individuals will undergo regular assessments including monitoring for treatment-emergent adverse events and serious adverse events up to approximately 108 weeks. Researchers will track safety by noting any adverse events that lead to permanent withdrawal from mezagitamab. The study includes physical evaluations, laboratory tests, and ongoing safety monitoring to understand how well participants tolerate the treatment and how effective it is over the long term.

Researchers are evaluating the long-term safety and effects of nerandomilast in people with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) who have previously completed treatment with nerandomilast in earlier studies. The study aims to understand how well participants tolerate nerandomilast over time, and whether it helps improve lung function, delays symptom worsening, reduces hospital visits, or impacts survival. This is a Phase 3 open-label extension trial. Participants take nerandomilast tablets daily for up to 1 year and 10 months while continuing their usual pulmonary fibrosis treatments. The study follows an open-label design where all participants receive nerandomilast. There are no placebo or comparator groups in this extension phase. Throughout the study, participants regularly visit their doctors for health assessments and lung function tests. Doctors monitor any health problems or side effects experienced during treatment. The main outcome measured is whether participants experience any adverse events up to the final follow-up visit, which occurs at week 99. This close monitoring helps evaluate the long-term safety and potential benefits of nerandomilast in this patient group.

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 investigating the safety and effectiveness of the investigational drug [225Ac]Ac-A9-3408 in adults with melanoma that has spread to other parts of the body or cannot be removed by surgery. This Phase 1-1b trial focuses on patients with unresectable or metastatic melanoma who have experienced disease progression despite prior anti-PD-1/PD-L1 treatment. The study aims to determine the side effects, the highest safe dose, and how the drug affects tumors and normal organs using dosimetry. Participants will receive the investigational drug intravenously every 6 weeks for up to 6 cycles. Before treatment, they will undergo a single intravenous diagnostic scan with [68Ga]Ga-A9T-3202 during screening. The Phase 1 part evaluates safety, tolerability, and dosimetry to select a recommended Phase 2 dose, while Phase 1b assesses safety, efficacy, and dosimetry at that dose. Throughout the study, participants will have regular doctor visits for checkups and tests. Researchers will monitor side effects, treatment-related adverse events, and tumor response. The main outcomes include identifying the maximum tolerated dose within the first 28 days and capturing any adverse events from the start of treatment until its end. Participants must be adults with adequate health status, and safety will be closely observed during the entire treatment period.

This research aims to evaluate the clinical benefit and safety of tabelecleucel for treating Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in patients who have undergone solid organ transplant (SOT) or allogeneic hematopoietic cell transplant (HCT) and have failed prior rituximab or rituximab plus chemotherapy treatments. The study focuses on participants with EBV+ PTLD after failure of rituximab alone or with chemotherapy, including subgroups based on chemotherapy eligibility and transplant type. Tabelecleucel, an off-the-shelf allogeneic T-cell immunotherapy, is given intravenously in 5-week cycles, with doses administered on Days 1, 8, and 15, followed by observation through Day 35. Treatment continues until maximal response, unacceptable side effects, new non-protocol therapy starts, or treatment failure. The study includes cohorts for solid organ transplant recipients (with or without chemotherapy) and hematopoietic cell transplant recipients, with up to 2 or 4 different HLA restrictions allowed, respectively. Participants undergo disease assessments including PET-CT or MRI scans to measure response, and safety is monitored throughout treatment. Follow-up lasts up to 5 years for some participants, with more frequent monitoring every 3 months for others, depending on enrollment timing and response. The primary outcome measured is the objective response rate over 2 years in different participant groups receiving commercial or comparable tabelecleucel products.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and preliminary effectiveness of AMO959 combined with lutetium (177Lu) vipivotide tetraxetan (AAA617) and an androgen receptor pathway inhibitor (ARPI) in adult males with PSMA-positive metastatic castration resistant prostate cancer (mCRPC). The study focuses on participants who have failed one prior ARPI treatment, with or without prior taxane chemotherapy exposure. The trial is a Phase Ib/II open-label study designed to assess these treatments in this specific patient population. The study includes two phases. Phase Ib involves dose escalation of AMO959 alone and then combined with AAA617 and ARPI (either abiraterone or enzalutamide) in small groups to determine safety, tolerability, and the recommended dose for expansion. Phase II randomizes participants into three groups to receive the recommended dose(s) of AMO959 plus AAA617 and ARPI or AAA617 plus ARPI alone. Treatment administration and dose escalation meetings occur during the initial phase to monitor safety and dosing. Participants will be closely monitored for adverse events, dose-limiting toxicities, dose adjustments, and drug exposure for up to 24 to 45 months depending on the phase. Effectiveness will be assessed by measuring biochemical response through PSA levels. Eligibility involves imaging to confirm PSMA-positive disease and specific disease progression criteria. The study also tracks drug tolerability and participant safety throughout the treatment and follow-up periods.

This trial investigates the safety and effectiveness of rilvegostomig combined with fluoropyrimidine and trastuzumab deruxtecan (T-DXd) compared to trastuzumab, chemotherapy, and pembrolizumab in adults with HER2-positive locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 with a combined positive score of 1 or higher. Additionally, rilvegostomig combined with trastuzumab and chemotherapy is studied separately to understand each component's contribution. This Phase 2, randomized, open-label, global study is conducted at 200-250 sites in about 25 countries. Participants are randomly assigned to one of three arms: Arm A receives rilvegostomig, fluoropyrimidine, and T-DXd; Arm B receives trastuzumab, chemotherapy, and pembrolizumab; Arm C receives rilvegostomig, trastuzumab, and chemotherapy. Treatments are administered mostly by intravenous infusion every three weeks, with capecitabine given orally twice daily. The study compares these treatment regimens to evaluate their effects on the cancer. Throughout the study, participants undergo assessments including tumor measurements, organ function tests, and heart function evaluation to ensure safety and monitor disease progression. The main outcomes measured are progression-free survival and overall survival for up to approximately six years. Researchers will also monitor adverse events and overall health status during and after treatment.

Researchers are evaluating different treatment strategies for patients hospitalized with Gram-negative bloodstream infections (GN BSIs) through the BALANCE+ trial. This adaptive platform trial uses an open-label, pragmatic design embedded in routine care to address important questions in managing GN BSIs, including antibiotic treatment duration, antibiotic de-escalation, oral antibiotic options, central line management, specific pathogen treatment, and follow-up blood cultures. The study builds on previous research and aims to improve patient outcomes and reduce antimicrobial resistance, a growing global health concern. The trial includes multiple treatment comparisons, such as de-escalation versus no de-escalation of antibiotics, oral beta-lactams versus non-beta-lactams, central vascular catheter retention versus replacement, cephalosporin versus carbapenem for low-risk AmpC organisms, and routine follow-up blood cultures versus no routine follow-up. Treatments are tailored based on blood culture results and clinical decisions, with specific protocols for antibiotic switching and catheter management. The trial uses Bayesian methods with interim analyses after every 1000 patients initially, then every 200 patients, and stops domains based on predefined criteria or sample sizes. Participants are patients admitted to hospitals with confirmed Gram-negative bacteremia who meet eligibility criteria for each domain. Assessments include monitoring for death, reinfection, readmission, and new antimicrobial resistance over 90 days, measured by the Desirability of Outcome Ranking (DOOR) scale. The trial incorporates detailed inclusion and exclusion criteria and collects data through routine clinical care, ensuring ongoing evaluation of treatment effectiveness and safety throughout the study period.