Murdoch

Researchers are evaluating 177Lu-RAD204, a radiolabeled antibody targeting PD-L1, in a Phase 01 study involving participants with advanced solid tumors that express PD-L1. The study aims to assess the safety, tolerability, biodistribution, radiation dosimetry, and preliminary anti-tumor effects of this treatment. The main goal is to find the maximum tolerated dose and recommended doses for future studies in participants with cancers such as NSCLC, SCLC, triple-negative breast cancer, melanoma, head and neck cancer, endometrial cancer, and others with specific genetic markers. The study includes a pre-screening period for PD-L1 testing if needed, followed by a screening period lasting up to four weeks. Participants undergo a Phase 0 Imaging Period where a low dose of 177Lu-RAD204 is given to assess imaging quality, safety, and dosimetry over two weeks. This may be followed by a Phase 1 Treatment Period with escalating doses of 177Lu-RAD204 administered in cycles lasting six weeks each. Participants may receive multiple treatment cycles based on clinical benefit and safety evaluations. Dose-limiting toxicity is monitored for six weeks after the first treatment dose, and dosing intervals may be adjusted as agreed by the study team. During the study, participants will have imaging scans, safety evaluations, and laboratory tests to track the distribution and effects of 177Lu-RAD204. Researchers will measure pharmacokinetics, radiation dosimetry, and tumor responses up to 30 weeks. Safety and tolerability are closely monitored throughout. Participants must meet specific health and tumor criteria to join and will be observed for any adverse reactions. The total duration of participation varies depending on treatment response and tolerability.

Researchers are studying metastatic castration-resistant prostate cancer mCRPC to find new treatment options. This trial evaluates if the study medicine ifinatamab deruxtecan I-DXd or MK-2400 helps people live longer overall and experience slower cancer growth or spread compared to chemotherapy. The study is a Phase 3 trial comparing I-DXd with standard chemotherapy for mCRPC patients. Participants are randomly assigned to receive either I-DXd at 12 mgkg every 3 weeks through intravenous infusion or docetaxel chemotherapy at 75 mgm2 every 3 weeks combined with daily prednisone pills. Treatment continues until the disease progresses, unacceptable side effects occur, or treatment is stopped for other reasons. Premedication is given before each dose of I-DXd to help prevent nausea and vomiting. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess overall survival and radiographic progression-free survival for up to about 36 months. Additional measures include response rates, time to pain progression, PSA progression, and adverse events. The study tracks safety, treatment effects, and quality of life over a long follow-up period to better understand the potential benefits and risks of I-DXd compared to chemotherapy.

Researchers are studying pulmonary arterial hypertension PAH, a condition where lung blood vessels become thick and narrow, causing high blood pressure in the lungs and making it hard for the heart to work. PAH can cause difficulty breathing and limit activity. While standard treatments help symptoms, they do not stop the disease from worsening. This research focuses on sotatercept, a targeted therapy aimed at specific proteins involved in PAH, to learn about its long-term safety and tolerability when added to usual PAH treatments. Participants in this long-term follow-up study, who previously took part in certain sotatercept trials, may continue receiving sotatercept by subcutaneous injection every three weeks. Those coming from blinded studies start at 0.3 mgkg with possible increases up to 0.7 mgkg, while those from unblinded studies continue their current dose with possible titration to 0.7 mgkg. The study monitors participants over an extended period to assess continued effects alongside their usual PAH therapy. During the study, participants will have regular assessments including monitoring for adverse events, blood tests for blood components and chemistry, body weight, blood pressure, and ECG readings. Researchers will also evaluate exercise capacity, heart function markers, and risk scores related to PAH. The study aims to follow participants for up to approximately 7 to 8 years to understand long-term safety, treatment tolerability, and health changes while using sotatercept with standard PAH care.

Primary immune thrombocytopenia ITP is a condition where the immune system mistakenly destroys platelets, leading to a lower number of platelets and increased risk of bruising or bleeding. This Phase 3 study evaluates the long-term safety, tolerability, and effectiveness of mezagitamab in adults with chronic primary ITP. The study also investigates how the body processes mezagitamab over an extended period. Participants who completed previous mezagitamab studies TAK-079-3002 or TAK-079-1004 will be invited to join this continuation trial. Eligible participants may receive mezagitamab injections on demand, with treatment courses repeated as needed based on specific criteria and the investigators clinical judgment. The treatment is administered subcutaneously. During the study, participants will visit the clinic several times for assessments. Researchers will monitor safety by tracking treatment-emergent adverse events, and evaluate effectiveness through platelet response and remission rates. Measurements of drug levels and antibodies will also be taken. The study may last up to approximately 108 weeks, allowing detailed long-term follow-up.

Researchers are studying people with idiopathic pulmonary fibrosis IPF or progressive pulmonary fibrosis PPF who have previously taken nerandomilast in another study. The aim is to assess how well patients tolerate long-term treatment with nerandomilast and to evaluate whether it improves lung function and delays worsening symptoms, hospital visits, or death. This open-label extension trial is sponsored by Boehringer Ingelheim and focuses on treatment over an extended period. Participants take nerandomilast tablets for up to 1 year and 10 months while continuing their usual pulmonary fibrosis treatments. The study involves a single treatment group receiving the drug, and no placebo or comparison groups. Regular visits with doctors help monitor health and collect data during this extended treatment phase. Throughout the study, participants undergo regular lung function tests and health assessments to track any adverse events and changes in lung capacity. The main outcome measured is the occurrence of any adverse events for up to about 99 weeks. Secondary outcomes include changes in forced vital capacity and time to worsening of disease symptoms or hospitalization. The study includes ongoing safety monitoring with a total participation time of up to nearly two years.

Researchers are evaluating whether retatrutide and tirzepatide can prevent major adverse liver outcomes in adults with metabolic dysfunction-associated steatotic liver disease MASLD who are at high risk based on non-invasive tests. This Phase 3 randomized controlled trial aims to assess these treatments compared to placebo in about 4,500 adults over approximately 224 weeks. The study is sponsored by Eli Lilly and Company and focuses on liver disease progression and related health measures. Participants will be randomly assigned to receive retatrutide, tirzepatide, or placebo, all administered by subcutaneous injection. The trial includes two placebo groups corresponding to each experimental drug. After completing the main study, eligible participants may join a 2-year extension where all will receive either retatrutide or tirzepatide regardless of their initial assignment. During the study, participants may attend around 25 to 30 clinic visits for health monitoring, study procedures, and assessments of liver function and disease status. Researchers will measure the time to major adverse liver outcomes, changes in liver fibrosis scores, liver stiffness, liver fat content, liver enzyme levels, body weight, and cardiovascular events. Monitoring will continue from baseline through study completion, with detailed evaluations at multiple timepoints including week 104.

Researchers are studying an investigational drug called 225AcAc-A9-3408 in adults with melanoma that cannot be removed by surgery or has spread to other parts of the body. The study aims to find out the side effects of this drug and identify the highest safe dose. It also examines how well the drug shrinks melanoma tumors and measures how much of the drug reaches normal organs and tumors. Participants receive an intravenous injection of the investigational drug once every 6 weeks, for up to 6 doses. Before treatment, they are given a single intravenous dose of the diagnostic agent 68GaGa-A9T-3202 during screening. The study includes two groups a dose escalation phase to find the recommended dose and a dose expansion phase to further evaluate safety and effectiveness at that dose. During the trial, participants visit the doctors office regularly for checkups, scans, and tests, including PET scans to measure drug uptake and tumor response. Researchers monitor side effects from the first treatment until the end of the study and assess tumor responses up to one year after enrollment. The study also tracks how the drug distributes in the body and its effects on organs. Total participation may last several months depending on the treatment cycles received.

Researchers are evaluating tabelecleucel, an off-the-shelf, allogeneic T-cell immunotherapy, for treating Epstein-Barr virus-associated post-transplant lymphoproliferative disease EBV PTLD after failure of rituximab or rituximab plus chemotherapy. This phase 3, multicenter, open-label study includes participants with EBV PTLD following solid organ transplant or allogeneic hematopoietic cell transplant. The study aims to determine the clinical benefit and safety profile of tabelecleucel in these patient groups. Participants receive intravenous tabelecleucel in 5-week cycles, with doses given on Days 1, 8, and 15, followed by observation through Day 35. Treatment continues until maximal response, unacceptable toxicity, initiation of other therapy, or tabelecleucel failure, with limits on the number of different HLA restrictions used. The study allows up to 5 years of follow-up for disease and survival status, with more frequent assessments for certain participants and responders. During the study, participants undergo regular assessments including imaging with PET-CT or MRI to measure disease response. Researchers monitor objective response rate, duration of response, overall survival, and rates of allograft loss or rejection. Safety and treatment effects are closely followed, and participants are observed for up to one year after initial response. The total study duration includes treatment cycles and extended follow-up to evaluate long-term outcomes.

Researchers are studying a treatment approach for adult men with PSMA-positive metastatic castration resistant prostate cancer mCRPC who have previously received one androgen receptor pathway inhibitor ARPI and may or may not have had taxane chemotherapy. This phase IbII trial aims to first evaluate the safety, tolerability, and how the body processes the drug AMO959 combined with lutetium 177Lu vipivotide tetraxetan AAA617 and ARPI. Then, it will assess the preliminary effectiveness of this combination in patients who have not yet been treated with taxane chemotherapy for mCRPC. The study includes two phases Phase Ib with small groups receiving escalating doses of AMO959 alone, then combined with AAA617 and ARPI abiraterone or enzalutamide to determine the recommended dose and Phase II where participants are assigned to treatment arms receiving AMO959 with AAA617 and ARPI, AAA617 with ARPI, or other dosing regimens. Treatments involve taking AMO959 twice daily for 14 days followed by combinations with AAA617 every six weeks for up to six cycles, along with continuous ARPI therapy. Participants will undergo safety monitoring for side effects and dose adjustments during treatment lasting up to about two years. The study measures include biochemical responses like PSA levels, progression-free survival, overall response rates, and quality of life assessments. Blood samples will track drug levels and radiation doses. Follow-up continues to monitor adverse events and disease progression for up to nearly four years from treatment start, with regular visits during treatment cycles.

Researchers are assessing the effectiveness and safety of rilvegostomig combined with fluoropyrimidine and trastuzumab deruxtecan 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 CPS 1. The study also evaluates rilvegostomig combined with trastuzumab and chemotherapy to understand the contribution of each treatment component. This is a Phase 2, randomized, open-label, global, multicenter trial sponsored by AstraZeneca. Participants are divided into three groups Arm A receives T-DXd, rilvegostomig, and fluoropyrimidine capecitabine or 5-FU Arm B receives pembrolizumab, trastuzumab, and chemotherapy either 5-FU plus cisplatin or capecitabine plus oxaliplatin Arm C receives rilvegostomig, trastuzumab, and chemotherapy 5-FU plus cisplatin or capecitabine plus oxaliplatin. Treatments are given by intravenous infusion every three weeks or oral administration twice daily for capecitabine. This setup allows comparison of different combinations to evaluate each drugs role. During the study, participants will be monitored for progression-free survival and overall survival up to about six years. Researchers will also assess response rates, duration of response, adverse events, pharmacokinetics, immunogenicity, and quality-of-life factors like eating difficulties and side-effect burden. The study involves regular assessments including tumor measurements and laboratory tests. Participation may last several years, with safety and efficacy closely followed throughout this time.