Southport

Researchers are investigating the drug bezuclastinib in an open-label, two-part Phase 2 study for patients with Advanced Systemic Mastocytosis (AdvSM), including Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL). The study aims to evaluate the safety, effectiveness, and how the drug behaves in the body for these serious conditions. Bezuclastinib is given orally as tablets taken continuously in 28-day cycles. The study has two parts: Part I focuses on identifying safe and tolerable doses of bezuclastinib over 18 months, while Part II evaluates its effectiveness by measuring the objective response rate and confirming the relationship between drug exposure and response during another 18-month period. Participants will undergo assessments including clinical evaluations, laboratory tests, and monitoring of their disease status to determine treatment effects and safety. Researchers will track the drug's impact on the disease and patient health throughout the study, which involves continuous treatment and follow-up over the specified time frames.

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 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 evaluating the safety, effectiveness, best dose, and how the body processes (pharmacokinetics) an investigational drug called BNT326. This study includes people with advanced solid tumors that are metastatic, recurrent, or have progressed after previous treatments. The investigation is divided into two parts: Part 1 tests BNT326 alone, and Part 2 studies BNT326 alone or combined with other immunotherapy drugs, including pumitamig (BNT327). Participants have specific tumor types like melanoma, non-small cell lung cancer, breast cancer, gastric cancer, colorectal cancer, and cervical cancer, among others. In Part 1, participants receive BNT326 by intravenous infusion in various groups based on cancer type and prior treatments. Part 2 involves BNT326 given alone or with pumitamig, also by intravenous infusion, in several defined cancer groups. Some groups are randomized to receive different dose levels or combinations to find the optimal treatment plan. The study includes a screening phase, treatment phase lasting up to 24 months or until progression or unacceptable side effects, a safety follow-up, efficacy follow-up, and long-term survival monitoring, totaling about 38 months for Part 1 and 48 months for Part 2. During the study, participants undergo regular assessments including measuring tumor response using RECIST criteria, monitoring for side effects and serious adverse events up to months after treatment ends, and measuring drug levels in the blood. Researchers track treatment interruptions or discontinuations due to side effects and evaluate dose-limiting toxicities. Tumor tissue samples are required before enrollment. Safety and effectiveness data are collected throughout treatment and follow-up periods to understand how well BNT326 works alone or combined and its safety profile.

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.

Researchers are evaluating the safety and effectiveness of the WiSE CRT System combined with an intracardiac pacemaker to achieve a totally leadless cardiac resynchronization therapy (CRT) for patients with heart failure. This is a single-arm, prospective, multicenter observational study focused on patients who meet specific guidelines for CRT implantation, including those with certain heart rhythm and heart function characteristics. The study aims to provide a leadless solution that may benefit patients with anatomical or infection-related concerns for traditional devices. Participants will receive the WiSE CRT System, an implantable device that provides left ventricular pacing stimulation, working together with an existing system that provides right ventricular pacing. Together, these devices deliver biventricular pacing to improve heart function. The study involves patients receiving either a new totally leadless CRT implant or an upgrade from a chronic intracardiac pacemaker to CRT. Treatment is delivered through device implantation, with follow-up visits scheduled to monitor outcomes. During the study, participants will be monitored for device- and procedure-related complications at 1 month and 6 months after implantation. Researchers will also assess biventricular capture using a 12-lead ECG at these same time points. Patients will provide consent and undergo assessments according to study protocols, with safety and effectiveness data collected throughout the follow-up period. The total duration and schedule of follow-up visits are designed to ensure careful observation of the devices' performance and patient health.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of IMP1734, a PARP1 selective inhibitor, in participants with advanced solid tumors. The study aims to assess preliminary efficacy and find the best dosing for future clinical development. This first-in-human trial is conducted in two parts, focusing on patients with recurrent, advanced, or metastatic solid tumors including metastatic prostate, ovarian, breast, and other solid tumors with specific genetic mutations. The trial has two main phases: Part 1 involves dose escalation of IMP1734 as a monotherapy to determine the maximum tolerated or achievable dose in solid tumors. Part 2 focuses on dose optimization to select the optimal dose for further clinical use. Treatment involves oral administration of IMP1734, with dose escalation steps and combination dose escalations in specific cancers like metastatic prostate cancer, ovarian, and breast cancer. Participants will undergo regular assessments to monitor safety through adverse event tracking, pharmacokinetic and pharmacodynamic evaluations, and tumor response measurements using criteria like RECIST1.1, CA125, or PSA. The study includes monitoring for serious adverse events from consent until 30 plus 7 days after the last dose. Dose-limiting toxicities are assessed during the first treatment cycle. Participants are expected to have adequate organ function, a life expectancy of at least 12 weeks, and will be followed closely during the trial to evaluate the drug's safety and potential anti-tumor activity.

Researchers are evaluating the safety and effectiveness of rilvegostomig compared to pembrolizumab, both combined with platinum-based doublet chemotherapy, as initial treatments for patients with metastatic non-squamous non-small cell lung cancer (mNSCLC) whose tumors express PD-L1. This Phase III, randomized, double-blind, global study focuses on patients whose tumors meet the PD-L1 expression threshold of 1% or higher and do not have certain genetic mutations or rearrangements that would require other targeted therapies. Participants receive either rilvegostomig or pembrolizumab intravenously on the first day of each 21-day treatment cycle. Both groups also receive platinum-based chemotherapy drugs such as carboplatin or cisplatin, administered intravenously up to four cycles, along with pemetrexed given intravenously on Day 1 of each cycle. The study monitors these treatments as first-line therapy for metastatic non-squamous NSCLC. During the study, participants undergo regular assessments including imaging scans to measure tumor size and response, as well as evaluations of organ and bone marrow function. Researchers track overall survival and progression-free survival for up to approximately five years. Safety is closely monitored throughout, and patients are followed long-term to assess outcomes related to treatment effectiveness and tolerability.

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab, both in combination with platinum-based doublet chemotherapy, as a first-line (1L) treatment for patients with squamous metastatic non-small cell lung cancer (mNSCLC) whose tumors express PD-L1 (tumor cells (TC) ≥ 1%).

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.