Baise

Researchers are conducting a first-in-human, open-label Phase I clinical trial to study HLX3902 in adults with metastatic castration-resistant prostate cancer mCRPC and other advanced solid tumors. The study aims to evaluate the safety, tolerability, and pharmacokinetic profiles of HLX3902 while also exploring preliminary efficacy in this patient population. This research is important for understanding how HLX3902 behaves in the body and its potential for treating advanced cancers. Participants will receive HLX3902 administered via intravenous infusion. The trial follows a dose escalation design to determine the maximum tolerated dose and observe any dose-limiting toxicities over treatment cycles lasting four weeks each. The study may continue up to approximately two years to monitor outcomes and drug effects. This trial is sponsored by Shanghai Henlius Biotech. Throughout the study, participants will undergo various assessments including safety monitoring, response evaluations, and laboratory tests. Researchers will measure adverse events, disease control, progression-free survival, and overall survival, as well as biomarkers such as prostate-specific antigen PSA and immune-related markers. Tumor tissue samples will be collected, and participants must agree to effective contraception. The total study duration extends until May 2028, with evaluations conducted regularly to track the treatments effects and participant health.

Researchers are evaluating the efficacy and safety of ZL-1310 compared to Investigators Choice Therapy in adults with relapsed Small Cell Lung Cancer SCLC. This phase 3, randomized, open-label study aims to compare treatment responses and overall survival between these two therapies in participants who have previously received platinum-based systemic therapy or tarlatamab. Participants are randomly assigned to receive either ZL-1310 as a single-agent drug or Investigators Choice Therapy, which includes Topotecan, Lurbinectedin, or Amrubicin. The study follows a parallel design and monitors participants during treatment and follow-up periods lasting up to 27 months to assess various outcomes. During the study, participants undergo regular evaluations including tumor assessments based on RECIST v1.1 criteria, brain metastases response evaluations, and quality of life measurements using validated questionnaires. Safety is closely monitored by tracking treatment-emergent adverse events. Participants are expected to comply with study procedures, including tumor biopsies or providing archived tissue samples, and the total study duration may extend to nearly three years.

This research aims to evaluate the clinical efficacy and safety of combining luspatercept with low-dose thalidomide compared to using luspatercept alone in adults with transfusion-dependent b2-thalassemia major. This inherited blood disorder requires regular red blood cell transfusions and has limited treatment options, making this study important for improving patient care. The trial is a prospective, multicenter, randomized, double-blind, placebo-controlled phase 2 study. Participants are randomly assigned in a 11 ratio to either receive luspatercept combined with low-dose thalidomide or luspatercept with a placebo. Luspatercept is given at a starting dose of 1.0 mgkg every 21 days, while thalidomide or placebo is given daily at 50 mg. Both treatments last for 48 weeks, and participants may continue best supportive care like transfusions, iron chelation, and other therapies as needed. The study includes a screening period, treatment phase, and follow-up at weeks 12, 24, 36, and 48. During the study, participants undergo physical exams, vital sign checks, blood tests, transfusion tracking, iron level monitoring, quality-of-life assessments, and safety evaluations. Researchers measure how well the treatment reduces the need for blood transfusions, with the primary outcome focusing on transfusion reduction between weeks 13 and 24. Secondary outcomes assess longer-term transfusion reduction, iron metabolism, hemolysis, and adverse events. Data is collected throughout the treatment and follow-up periods for detailed analysis.

Acute respiratory distress syndrome (ARDS) poses a major threat to public health and consumes substantial healthcare resources. Based on the National Hospital Quality Monitoring System (HQMS), our group found that more than 2.5 million patients with ARDS are admitted to intensive care units (ICUs) annually in China, resulting in total hospitalization costs of approximately RMB 29.32 billion. The in-hospital mortality rate is about 39%, which is substantially higher than the international average (12-37%). Extracorporeal membrane oxygenation (ECMO) represents the most important rescue therapy for patients with moderate-to-severe ARDS; however, mortality among ARDS patients receiving ECMO support remains as high as 60%. Therefore, reducing mortality in moderate-to-severe ARDS is essential for achieving the goals of the Healthy China 2030 Initiative. Inflammatory and immune dysregulation occurs in 38.7-70% of patients with ARDS, frequently leading to multiple organ dysfunction. Despite ECMO support, mortality among patients with severe ARDS remains extremely high. Three major challenges contribute to poor outcomes. First, immune dysregulation under ECMO support significantly increases the incidence and mortality of severe complications, while targeted therapeutic strategies based on underlying mechanisms are lacking. Second, the marked heterogeneity of ARDS complicates the identification of optimal timing and modalities of ECMO support. Third, the effects of different invasive mechanical ventilation strategies on lung injury and repair remain poorly understood, and mechanism-guided precision ventilation approaches are still unavailable. Building upon the largest ARDS and ECMO clinical-biological database in China established by our group, this project aims to develop a Chinese precision management strategy for ECMO-supported patients with moderate-to-severe ARDS. 1. Comprehensive characterization of immune spatiotemporal dynamics in moderate-to-severe ARDS is essential for identifying therapeutic targets Current biomarkers reflecting disease progression in ARDS are largely limited to static clinical parameters and single-dimensional measurements, making biomarker-guided precision therapy difficult. Previous studies have identified biomarkers such as soluble receptor for advanced glycation end-products (sRAGE), angiopoietin-2 (Ang-2), and surfactant protein D (SPD) as prognostic indicators, yet these markers provide limited mechanistic insights and have not translated into individualized therapeutic strategies. Our group has established the largest ARDS and ECMO biospecimen cohort in China and has preliminarily characterized the spatiotemporal immune landscape of moderate-to-severe ARDS. We identified VCAM1 and tRF-5004b as potential immune-related targets closely associated with disease progression, providing a solid foundation for the proposed study. 2. Elucidating inflammatory and immune mechanisms underlying severe ECMO-related complications is critical for targeted intervention Among ARDS patients receiving ECMO support, the incidence rates of acute kidney injury (AKI), bleeding/thrombosis, and infection are approximately 45.7%, 40.2%, and 44.7%, respectively. Systemic inflammatory and immune dysregulation is considered a major contributor to these complications, although the underlying mechanisms remain unclear. In addition to the excessive inflammatory response characteristic of ARDS, restoration of oxygen delivery after ECMO initiation may trigger bursts of reactive oxygen species, calcium overload, and endothelial injury, thereby exacerbating inflammation and causing multiple organ dysfunction. Clarifying these mechanisms is essential for developing individualized interventions against severe ECMO-related complications. 3. Establishing multidimensional ARDS subphenotypes provides the basis for precision awake ECMO therapy ARDS is highly heterogeneous with respect to etiology, clinical manifestations, pathophysiology, and molecular characteristics, resulting in variable responses to ECMO support. Conventional classification based on oxygenation or isolated physiological parameters fails to capture the complex biological and immunological evolution of the disease. Our group previously identified hyperinflammatory and hypoinflammatory ARDS phenotypes using multidimensional clinical and biological data, but differences in ECMO responsiveness between these phenotypes have not been systematically investigated. Therefore, comprehensive characterization of ARDS biological heterogeneity and development of an integrated subphenotyping model incorporating clinical, physiological, imaging, and immune molecular features are required to identify patients most likely to benefit from awake ECMO. 4. Deciphering mechanisms of lung injury and repair is crucial for individualized mechanical ventilation strategies Inappropriate mechanical ventilation can exacerbate ventilator-induced lung injury and impair lung repair. Understanding the cellular and molecular mechanisms underlying lung injury and regeneration and clarifying the relationship between ventilatory parameters and tissue stress responses are fundamental to achieving personalized lung-protective ventilation. This project will integrate multimodal imaging, respiratory mechanics, and multi-omics data to characterize the dynamic processes governing lung injury and repair in ARDS, thereby establishing precision mechanical ventilation strategies to enhance lung protection and promote tissue recovery. Perspectives and Expected Impact Focusing on the major challenges in the management of moderate-to-severe ARDS, this project will elucidate the mechanisms responsible for severe complications during ECMO support, establish a multidimensional phenotyping framework to identify patients most likely to benefit from awake ECMO, and decode the mechanisms of lung injury and repair to develop individualized ventilation strategies. Ultimately, this work will provide a comprehensive precision management framework for ECMO-supported ARDS patients, improve the standard of care for moderate-to-severe ARDS in China, and reduce disease-related mortality.

This research aims to evaluate the effectiveness and safety of the Isa-VRd regimen, combining Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone, in patients newly diagnosed with multiple myeloma who are not eligible for transplant. The study focuses on real-world use in China with a planned enrollment of 333 patients aged 18 and older. It explores important outcomes like complete response rates and minimal residual disease negativity. Participants will receive Isatuximab intravenously in an induction phase lasting 8 cycles of 4 weeks each about 32 weeks total. Dosing schedules include weekly and biweekly treatments depending on the cycle, along with subcutaneous Bortezomib injections, oral Lenalidomide daily with dose adjustments based on kidney function, and oral Dexamethasone on specific days. After induction, the treatment regimen may be adjusted by investigators, followed by a maintenance phase and long-term follow-up. During the study, participants will undergo regular assessments to monitor treatment effectiveness, including response evaluations each cycle and periodic minimal residual disease testing at months 8, 14, 20, and 26. Safety monitoring includes tracking adverse events throughout treatment and follow-up, which lasts up to 24 months. The study records additional outcomes such as survival rates and time to disease progression to better understand the treatments impact.