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Improving neuraminidase content of influenza vaccines is a major focus of vaccine development. Here the authors present safety and immunogenicity of seasonal influenza mRNA vaccine candidates simultaneously encoding hemagglutinin and neuraminidase antigens in a first in-human study.

Preliminary results from an investigator-initiated clinical trial showed that an AAV-OTOF gene therapy was safe and led to hearing improvements in ten patients with congenital deafness with 6–12 months of follow-up, including in a teenager and a young adult, expanding the age range from previous trials.

Here, the authors investigate the effect of perioperative levosimendan on postoperative subclinical heart failure, evaluated via NT-proBNP measurements in cardiac risk patients undergoing noncardiac surgery, and show no significant difference between levosimendan and placebo on the postoperative maximum NT-proBNP release.

Surgical nerve injuries can cause significant morbidity, yet no approved fluorescent agents exist for visualization. Here, the authors show in a Phase I multi-site trial that bevonescein was safe, established optimal dosing and timing, and provided a fluorescence signal for intraoperative nerve identification.

Vaccination provides protection from COVID-19, but optimization in design and route is an ever-ongoing process. Here the authors pursue an open-label, multi-arm phase I clinical trial to report the safety of a multi-valent, aerosol vaccine administered via inhalation, as well as superior mucosal immunity induced by ChAd over HuAd vectors.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

Borcoman and colleagues present the efficacy and safety results of the phase 2 PEVOsq basket trial investigating the combination of pembrolizumab with the epidrug vorinostat in patients with recurrent and/or metastatic squamous cell carcinoma.

In a reverse-translational study followed by a clinical trial, the targeting of antigen-presenting mast cells was identified as a therapeutic approach to overcome anti-PD-1 resistance in patients with metastatic triple-negative breast cancer who experienced clinical benefit when treated with the mast cell stabilizer cromolyn.

This study integrates polygenic risk scores with four emulated clinical trials using FinnGen data and shows the feasibility of this approach while highlighting potential pitfalls.

In a cluster-randomized trial conducted across 70 medical centers in six countries, a 16-week structured educational program for healthcare providers improved adherence to guidelines for rhythm control but not for stroke prevention in individuals with atrial fibrillation.

A large international panel of experts reach consensus on a new standard for reporting settings in psychedelic trials, identifying 30 key non-pharmacological factors to strengthen the rigor of psychedelic research.

Pleural spread or recurrence of thymic epithelial tumors (TETs) needs further exploration in clinics and there is currently no recognized effective treatment. Here this trial evaluates the perioperative and short-term outcomes of cytoreductive surgery and hyperthermic intrathoracic chemotherapy (S-HITOC) for TETs with pleural spread or recurrence.

In a phase 1/2 trial in patients with advanced non-small-cell lung cancer (NSCLC), followed by a phase 2 trial in an EGFR-mutant selected population, treatment with the TROP2-targeting antibody–drug conjugate sacituzumab tirumotecan led to encouraging clinical response rates, especially in patients with EGFR-mutant NSCLC, which was supported by mechanistic data.

A single dose of the anti-sporozoite monoclonal antibody CIS43LS can achieve durable, sterile protection against Plasmodium falciparum infection.

Neoadjuvant cancer therapeutic strategy has been explored in phase I/II clinical studies for head and neck squamous cell carcinoma. Here this group reports a single-arm, phase II clinical trial evaluating the neoadjuvant radiotherapy plus PD-1 inhibitor tislelizumab combined with paclitaxel and cisplatin, followed by radical surgical resection on 28 patients with untreated stage III-IVB head and neck squamous cell carcinoma.

In the IMpower151 trial, the drug combination previously shown to be effective in the IMpower150 trial was not significantly effective in a Chinese population.

While anti-retroviral therapy (ART) helps contain HIV, whether adoptive T cell therapy further improve the prognosis is unclear. Here the authors conduct an open-label, single-arm phase 1 study to assess the safety (primary outcome) and characteristic (secondary outcome) of autologous, HIV-specific T cell therapy to find it safe to warrant further efficacy assessment.

Up to 25% of patients with ALK-rearranged non-small cell lung cancer (NSCLC) experience disease progression within the first year of targeted therapy. This work reports a phase 2 trial investigating whether combining alectinib with bevacizumab can delay resistance mechanisms in advanced ALK-rearranged NSCLC.

Tacrolimus is a critical immunosuppressant for liver transplant recipients, but its dosing is challenging due to individual variability. Here, the authors show that a phenotypic personalized medicine approach improves tacrolimus dosing precision, reducing large deviations from target levels and shortening hospital stays in a Phase 2 randomized trial.

The current use of immune checkpoint inhibitors without chemotherapy on patients with metastatic breast cancer (MBC) has not proven useful. Here this group reports a phase 2 NIMBUS trial evaluating the efficacy/safety of nivolumab + low dose ipilimumab in 30 patients with hypermutated HER2-negative MBC.

The clinical activity of neoadjuvant immunochemotherapy for treating locally advanced oral squamous cell carcinoma (LA-OSCC) remains uncertain. In this single-arm, phase II trial, the authors show that neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin provides a favourable pathological response and manageable safety in patients with LA-OSCC while baseline CD4_Tfh_CXCL13 cells may serve as a predictive biomarker of efficacy.

In a multicenter, open-label, randomized phase 2 trial, neoadjuvant chemoradiation with PD-1 blockade elicited a pathological complete response rate superior to that with neoadjuvant chemoradiation alone in patients with locally advanced rectal cancer.

SPIRIT 2025 provides updated guidance to authors, reviewers and editors, when preparing clinical trial protocols to enhance their transparency and completeness.

Effective treatments for atopic dermatitis (AD) are highly sought after. Here the authors develop ucenprubart (LY3454738) for treating AD and find, in a randomized, multiple arms, multicenter, placebo controlled, and dose-escalating phase 1 trial (NCT03750643) trial, ucenprubart to be safe and showing preliminary efficacy when compared with placebo at 12 weeks post treatment.

In this randomized double-blind controlled trial, the authors examine whether the combination of transcranial direct current stimulation and exposure–response prevention (ERP) is more effective than ERP alone at improving OCD symptoms.

CONSORT 2025 provides updated guidance to authors, reviewers and editors, when writing and evaluating manuscripts of randomized trials to ensure that trial reports are clear and transparent

The core circadian transcription factor BMAL1 regulates circadian-dependent myocardial injury.

Italiano and colleagues assess the efficacy and safety of treatment of gastroenteropancreatic neuroendocrine neoplasms with regorafenib plus avelumab and explore biomarkers with resistance prediction value, such as programmed death 1 and indoleamine 2,3-dioxygenase 1 expression and activity.

This study reveals that in people with first episode of psychosis receiving oral antipsychotic medication, switching to long-acting injectable antipsychotic therapy may reduce psychotic relapses, especially in vulnerable subgroups, such as those with prior relapses or non-adherence to antipsychotic medication.

Kim and colleagues perform a phase 2 clinical trial (ELM-2) of odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma and report on the primary analyses of the efficacy and safety profile.

The use of a standardized outcome metric enhances clinical trial interpretation and cross-trial comparison. Here, the authors show the implementation of such a metric using type 1 diabetes trial data, reassess and compare results from these trials, and extend its use to define response to therapy.

In a multicenter randomized phase 3 trial, stapokibart, a humanized monoclonal antibody that targets IL-4R alpha, significantly improved daily nasal and ocular symptom scores during the pollen phase in patients with moderate-to-severe seasonal allergic rhinitis.