Browse Articles

Sunvozertinib monotherapy versus platinum-based chemotherapy as first-line treatment for advanced NSCLC with EGFR exon20ins: Primary analysis of a multinational phase 3 randomized study (WU-KONG28).

LBA8500 Background: Sunvozertinib has been granted accelerated approval in the US and China for the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor exon 20 insertion mutations (EGFR exon20ins) who failed platinum-based chemotherapy, based on results from two phase 2 single arm pivotal studies (WU-KONG1B [NCT03974022] and WU-KONG6 [NCT05712902]). WU-KONG28 (NCT05668988) is a multinational randomized confirmatory phase 3 study to compare sunvozertinib versus platinum-based chemotherapy as first-line treatment in advanced NSCLC patients with EGFR exon20ins. Here we reported the primary analysis of WU-KONG28 study results. Methods: Eligible patients were randomized in a 1:1 ratio, stratified by baseline brain metastasis status, to receive either sunvozertinib 300 mg once daily or chemotherapy (carboplatin [AUC5] and pemetrexed [500 mg/m²]) once every 3 weeks for up to 6 cycles, followed by pemetrexed maintenance therapy until disease progression or other discontinuation criteria were met. Patients in the chemotherapy arm could cross over to receive sunvozertinib upon confirmed progressive disease by the blinded independent central review (BICR). The primary endpoint was progression free survival (PFS) assessed by BICR per RECIST 1.1. Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DoR), and safety profile. PFS and OS were analyzed using log-rank test and Cox proportional hazards model. The data cutoff date was Jan 16, 2026. Results: A total of 324 patients were randomized to receive sunvozertinib (N=163) or chemotherapy (N=161). Baseline characteristics were generally balanced between the two arms. PFS by BICR was significantly longer with sunvozertinib than chemotherapy (median: 10.3 vs 7.5 months; hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.50, 0.85, p=0.0008). The PFS benefit was consistent in trends across subgroups. In the chemotherapy arm, 90.2% of patients with BICR-confirmed disease progression crossed over to receive sunvozertinib. The OS data were immature. Patients in the sunvozertinib arm showed higher confirmed ORR (58.9% vs 31.1%) and longer median DoR (11.2 vs 7.1 months). Safety profile of sunvozertinib was similar to what was previously reported. Drug-related treatment emergent adverse events (TEAEs) leading to treatment discontinuation occurred in 7.4% of patients. No drug-related TEAE leading to fatal outcome was reported. Conclusion: Sunvozertinib demonstrated significantly superior antitumor efficacy than chemotherapy with a manageable safety profile. These results support sunvozertinib as a first-line treatment for advanced NSCLC harboring EGFR exon20ins. Clinical trial information: NCT05668988 .

GATHeR: graph-based accurate tool for immunoglobulin heavy- and light-chain reconstruction

Abstract Recovering full-length, paired B-cell receptor (BCR) sequences from scRNA-seq reads remains difficult, especially in naive and memory B cells where immunoglobulin transcripts are sparse. Incomplete constant-region coverage in current methods limits isoform, subclass, and allele resolution. Here we present GATHeR, an open-source tool that assembles and annotates paired heavy- and light-chain BCR sequences and extends assembled sequences into constant regions. This enables confident subclass and allele assignment and recovery of membrane-bound isoforms, including the transmembrane segment and cytoplasmic tail, thereby distinguishing surface BCRs from secreted antibodies. GATHeR supports Smart-seq2/3 and 10x Genomics libraries and outperforms existing methods across benchmarks, with the largest gains in naive and memory B cells. Notably, in these populations the constant-region extension also enables detection of splice variation, including intron-containing heavy-chain transcripts with read-level support. By delivering high-fidelity receptor, isoform, and clonal lineage information, GATHeR broadens the analytical reach of scRNA-seq for B-cell immunology.

A Tetrahedral Silver-Rich Supercluster Composed of 8-Electron IrH ₂ Ag ₁₂ Icosahedra

Integrated experimental and life cycle assessment of biodiesel production from Datura stramonium seed oil using a one-pot sulfonated corncob catalyst

Abstract This study presents a combined experimental and life cycle assessment of the production of biodiesel from Datura stramonium ( DS) seed oil, using a one-pot sulfonated corn-cob solid acid catalyst. The catalyst, synthesized through simultaneous hydrothermal carbonization and sulfonation using sulfuric acid (H₂SO₄), was characterized by Fourier Transform Infrared Spectroscopy (FTIR), showing -SO₃H functionalization; X-ray Diffraction (XRD), indicating an amorphous carbon structure; and Brunauer-Emmett-Teller (BET) surface analysis showed 1.53 m 2 /g surface area, while the catalyst acidity was determined by titration, yielding 1.79 mmol/g. The esterification/transesterification process was optimized to achieve a conversion of 91.35% at 8.75 wt% catalyst loading, 63.2 °C, and 4.8 h(h) reaction time. A cradle-to-gate life cycle assessment (LCA) was performed according to ISO 14040/14044 with Ecoinvent 3.11 APOS system model integrated in OpenLCA 2.5 and the ReCiPe 2016 (H) method for 18 midpoint impact categories. The major environmental hotspots were associated with electricity and solvent consumptions for catalyst sulfonation, oil extraction, and esterification. The measured climate change potential for 17 experimental runs was in the range of 15.40 kg CO₂-eq (minimum impact) to 84.75 kg CO₂-eq (maximum impact), while terrestrial acidification was in the range of 0.129 kg SO₂-eq to 0.239 kg SO₂-eq. In the optimised condition, 15.70 kg CO₂-eq and 0.1306 kg SO₂-eq were obtained, which showed that a proper balance exists between high conversion and low environmental burden, thus confirming the use of corn cob derived acid catalysts for sustainable biodiesel production towards the circular bioeconomy.

NHS-Galleri: Primary results from a randomised controlled trial to assess the clinical utility of a multi-cancer early detection (MCED) test in population screening.

LBA100 Background: MCED blood tests can detect a shared cancer signal from circulating cell-free DNA. NHS-Galleri (NCT05611632) is a randomised controlled trial in England of 142,924 enrolled participants evaluating the clinical utility of an MCED test (Galleri) for annual screening of asymptomatic individuals aged 50–79 yrs. Methods: Peripheral blood samples were taken at up to 3 annual visits (Y0, Y1, Y2). After the Y0 blood draw, participants were randomised 1:1 to the intervention (I; blood tested by MCED test) or control (C; blood not tested) arms. I arm participants with a cancer signal detected MCED test result were referred into the NHS for diagnostic workup via appropriate urgent suspected cancer pathways. As agreed with NHS England, clinical utility was assessed by reduction in late stage (Stage III/IV [primary objective] and Stage IV [key secondary objective]) cancer incidence in I vs C arm ~3 yrs after the last participant’s randomisation. Results: Trial arms were well balanced. The primary endpoint of statistically significant Stage III/IV reduction in 12 prespecified cancers was not met (706 vs 688; incidence rate ratio [IRR] 1.03; Table). In these 12 cancers, Stage III/IV decreased from the prevalence screening round (IRR 1.19) to incidence rounds (0.95; 0.88). A 14% reduction in Stage IV cancers (342 vs 397) was observed after 3 yrs of screening (Y0: 9%; Y1: 22%; Y2: 26%). Stage I/II cancers increased by 16% (647 vs 559; relative risk [RR] 1.16 [1.03, 1.30]) after 3 yrs of screening. Similarly, Stage I-III cancers increased by 19% (1007 vs 846; RR 1.19 [1.09, 1.30]). Across all cancer types, 3637 and 3400 were diagnosed in I and C arms, respectively, over 3 yrs of screening. MCED quadrupled the number of screen-detected cancers (1173 vs 290). MCED reduced clinically-detected cancers by 21% (2464 vs 3110) and emergency presentations by 21% (225 vs 286). Aggregate test performance (99.55% specificity, 52.0% positive predictive value, 92.5% top-two and 87.0% top-one cancer signal origin accuracy) was consistent with prior studies and real-world evidence. There were 381 and 333 related adverse events (AEs) in I and C arms, respectively, and no related serious AEs. Conclusions: Although the primary endpoint was not met, adding annual MCED testing to standard-of-care cancer screening substantially increased screen-detected cancers and reduced Stage IV cancers and emergency presentations. This evidence combined with the favourable safety profile and robust performance suggests that integrating MCED into population screening programs may help reduce late stage cancer burden. Clinical trial information: NCT05611632 . Late-stage IRR (I/C) of 12 prespecified cancers. Stage III/IV Stage IV Y0 1.19 (95% CI: 0.98, 1.43) 0.91 (0.71, 1.18) Y1 0.95 (0.77, 1.17) 0.78 (0.57, 1.06) Y2 0.88 (0.73, 1.07) 0.74 (0.57, 0.95) Overall 1.03 (0.92, 1.14)p=0.6324 0.86 (0.744, 0.998)

Fluorescence localization and tracking imaging with a spectral-splitting perovskite single-pixel detector

Combining Ag(II) and Ag(I) Reactivity Enables Electrophotochemical Acyl Fluoride Installation on (Hetero)Arenes

Family planning practice among women living with human immunodeficiency virus in Magway, Myanmar: a cross-sectional study

First interim analysis of SWOG S1823: Operating characteristics of circulating microRNA 371a-3p (miR371) in predicting active germ cell malignancy (aGCM) in patients (pts) with early-stage testicular cancer.

LBA5003 Background: Circulating miR371 has been reported in retrospective studies as a biomarker with high accuracy for predicting aGCM. However, large prospective data of miR371 in identifying early stage disease are missing. S1823/GCC.1 (NCT04435756) is an international prospective cohort study designed to define the operating characteristics of plasma miR371 in detecting tumor relapse in pts with early stage aGCM managed with active surveillance (AS). Methods: Serial plasma samples for miR371 assessment were obtained within 56 days from new diagnosis of GCM (baseline) and every 6-12 months (according to risk of relapse) during AS, for maximum 3 years or until relapse. Samples most proximate to relapse were analyzed. Control pts were histology-matched 2:1 to cases. miR371 was measured by RT-PCR and expression was analyzed both qualitatively and quantitatively. Sensitivity, specificity, positive and negative predictive value (PPV and NPV) were evaluated to define miR371 operating characteristics. Results: 948 eligible pts were enrolled from June 2020 to May 2024 (median f/u= 32.7 months). The CSI and IIA pts managed with AS (n=630) formed the cohort of interest. At the time of data cutoff, 103 pts (16.3% overall; 14.7% of seminoma; 19.3% of nonseminoma) had relapsed. Results are from the 224 pts selected for the pre-specified interim analysis. PPV/NPV for the whole cohort was 0.66 (95% CI: 0.51, 0.80)/0.90 (95% CI: 0.88, 0.92), for seminoma 0.58 (95% CI: 0.36, 0.80)/ 0.92 (95% CI: 0.90, 0.94), for nonseminoma 0.75 (95%CI: 0.58, 0.92)/0.86 (95% CI: 0.83, 0.89). Sensitivity increased with stage at relapse (IIA,IIB, IIC/III) (p = 0.07) (Table). Conclusions: S1823 achieved the primary objective of defining the operating characteristics of plasma miR371 during AS. In aggregate, S1823 results showed high specificity and NPV suggesting potential clinical utilities of miR371 in managing pts with germ cell tumors. Future miR371-informed interventional trials to integrate miR371 in clinical practice are either underway or planned. Clinical trial information: NCT04435756 . Operating characteristics of miR371. Group N (Cases; Controls) Sensitivity (95% CI) Specificity (95% CI) Median time to relapse (mo) 1 Median miR371 at relapse (log RQ) 2 Overall 224 (69; 155) 0.54 (0.42, 0.65) 0.94 (0.90, 0.97) 5.8 17.17 Seminoma 108 (33; 75) 0.52 (0.35, 0.69) 0.93 (0.88, 0.99) 7.4 16.89 Nonseminoma 116 (36; 80) 0.56 (0.39, 0.72) 0.94 (0.88, 0.99) 5.3 17.50 Low-risk 184 (48; 136) 0.52 (0.38, 0.66) 0.93 (0.89, 0.98) 6.6 17.15 Moderate-risk 40 (21, 19) 0.57 (0.36, 0.78) 0.95 (0.85, 1.00) 4.1 17.27 Stage at Relapse 3 IIA 23 0.39 (0.19, 0.59) — 6.8 16.89 IIB 28 0.57 (0.39, 0.76) — 5.7 17.32 IIC/III 16 0.69 (0.46, 0.92) — 5.3 17.37 1 From orchiectomy; 2 Amongst miR371+ cases; RQ: relative expression; 3 Stage at relapse unavailable for 2 pts whose relapse was identified by STM only.

Interfacial proton-electron donor synergy enables sustainable oxime electrosynthesis via dual-path reduction

Transmembrane Domain Oligomerization and Intracellular Domain–Lipid Interaction Oppositely Modulates OX40 Receptor Activation Unveiled by ¹⁹ F NMR

Privacy-preserving federated learning for interpretable student at-risk prediction across schools

Giredestrant (GIRE) + palbociclib (PALBO) vs letrozole (LET) + PALBO as first-line (1L) therapy in patients (pts) with estrogen receptor–positive, HER2-negative locally advanced or metastatic breast cancer (ER+, HER2– LA/mBC): Primary analysis of the phase III persevERA BC trial.

LBA1006 Background: The combination of endocrine therapy (ET) with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is the current standard of care (SOC) for 1L treatment of pts with ER+, HER2– LA/mBC. GIRE, a next-generation oral selective full ER antagonist and degrader, has shown superior efficacy vs SOC ET in the adjuvant setting (lidERA BC; Bardia SABCS 2025) and in combination with everolimus vs SOC ET + everolimus in the post-CDK4/6i LA/mBC setting (evERA BC; Mayer ESMO 2025). Primary analysis results of persevERA BC (NCT04546009) are presented. Methods: Pts with de novo mBC or recurrent LA/mBC, measurable disease/evaluable bone disease, and no prior systemic LA/mBC therapy were randomized 1:1 to GIRE (30 mg daily [QD]) + LET placebo (QD) + PALBO (125 mg QD on Days 1–21) or LET (2.5 mg QD) + GIRE placebo (QD) + PALBO on each 28-day cycle (with a luteinizing hormone-releasing hormone agonist in pre-/peri-menopausal women, and men). The primary endpoint was investigator-assessed progression-free survival (INV-PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DoR), clinical benefit rate (CBR), and safety. Results: 992 pts were randomized (495 to GIRE; 497 to LET). Median age was 63.0 years; 80.1% were post-menopausal; 19.1% had de novo mBC; 69.3% had recurrent disease with treatment-free interval (TFI) >12 months (mo); 60.4% had visceral disease. At data cutoff (01/30/26), median follow-up was 52.2 mo and 623 INV-PFS events were observed. The hazard ratio (HR) for INV-PFS was 0.89 (95% confidence interval [CI] = 0.76, 1.05; p = 0.1553); median INV-PFS was 33.1 mo with GIRE + PALBO vs 28.2 mo with LET + PALBO (Δ 4.9 mo) (Table). The most common grade 3–4 adverse events (AEs) in the GIRE arm were hematologic abnormalities associated with PALBO. ET discontinuations due to AEs were similar (6.5% with GIRE vs 5.5% with LET). Conclusion: 1L GIRE + PALBO resulted in a numerical improvement in INV-PFS vs LET + PALBO in ER+, HER2– LA/mBC, though it did not meet pre-defined statistical significance. The safety profile was tolerable, consistent with individual agents, with no unexpected findings. The ongoing 1L pionERA BC study (NCT06065748) is exploring GIRE vs fulvestrant, in combination with physician’s choice of CDK4/6i in pts who have relapsed on adjuvant ET or with <12 mo TFI. Clinical trial information: NCT04546009 . GIRE + PALBO(n = 495) LET + PALBO(n = 497) Median PFS, mo (95% CI) 33.1 (30.2, 38.3) 28.2 (25.0, 33.1) HR* (95% CI); p-value † 0.89 (0.76, 1.05); 0.1553 Median OS, mo (95% CI) NE (NE) NE (61.3, NE) HR* (95% CI); p-value † 1.03 (0.83, 1.28); 0.777 ORR, % 60.2 58.8 Median DoR, mo (95% CI) 38.5 (30.4, 48.7) 30.4 (25.3, 36.1) HR* (95% CI); p-value † 0.80 (0.63, 1.01); 0.056 CBR, % 82.6 82.1 *Stratified. † Stratified log-rank. NE, not evaluable.

Navigating adoption barriers for microbial proteins in future food

Abstract Microbial biomass fermentation, in which microbes are cultivated to produce nutrient-dense biomass, offers a scalable route to sustainable protein production with low land, water, and greenhouse gas footprints. However, its shift from a speciality to a mainstream food continues to be difficult. Here, we move beyond technological overviews and propose a three-phase adoption framework: novelty barrier, early trust-building, and mainstream normalisation. This framework organises techno-economic, regulatory, and infrastructural barriers into a single trajectory. We trace single-cell proteins’ rise, decline and resurgence, map engineering and policy enablers by phase, and outline levers to move microbial proteins into resilient food systems.

Unlocking Multi–Product Selectivity in Olefin Electro-oxidation through Cooperative Cation/Oxygen Species Modulation

Striatal cAMP Is Regulated by a Local Clock-Gene-Dependent Mechanism

Feasibility and performance evaluation of a robotic steerable endoscopic submucosal dissection knife (with video)

Pathological complete response and ctDNA analyses in SCIENCE: Results from a randomized, phase III trial of neoadjuvant chemotherapy plus sintilimab and chemoradiotherapy plus sintilimab versus chemoradiotherapy in resectable locally advanced esophageal squamous cell carcinoma.

LBA4082 Background: The optimal neoadjuvant strategy for resectable locally advanced esophageal squamous cell carcinoma (RLA-ESCC) remains unclear. SCIENCE is a randomized phase III trial comparing neoadjuvant chemotherapy (nCT) plus sintilimab (S), neoadjuvant chemoradiotherapy (nCRT) plus S, and nCRT in RLA-ESCC, aiming to determine whether immunotherapy-based neoadjuvant therapy can improve efficacy without increasing toxicity or compromising surgical feasibility, and to explore ctDNA as an early molecular marker of treatment response. Methods: Pts with histologically confirmed, resectable thoracic ESCC (cT1N2–3M0 or cT2–4aN0–3M0 per AJCC/UICC 8th) were randomized 1:1:1 to nCT + S (A), nCRT + S (B), or nCRT (C), followed by surgery 6–8 weeks after neoadjuvant therapy. Co-primary endpoints were pCR and EFS. Longitudinal ctDNA was assessed (tumor-informed, personalized assay) at baseline, on-treatment, and preoperatively. pCR and EFS were compared using chi-square and log-rank tests, respectively, with overall two-sided α=0.05 controlled by allocating 0.02 to pCR and 0.03 to EFS. Interim analysis for pCR was prespecified. Results: At the time of data cutoff (Jan 19, 2026), 307 pts had completed neoadjuvant therapy and undergone surgery and were evaluable for pCR (Group A/B/C: 100/103/104). Most pts were male (88.3%) and had clinical stage III disease (81.4%). R0 resection was achieved in 303 pts (99 (99.0%) Group A; 102 (99.0%) Group B; 102 (98.1%) Group C). pCR rates were 18.0% in Group A, 57.3% in Group B, and 49.0% in Group C. Compared with Group A, pCR was significantly higher in Group B (OR 6.1, 95% CI 3.3–11.9; p<0.0001) and Group C (OR 4.4, 95% CI 2.3–8.5; p<0.0001). The safety profile was tolerable across three arms. Among 92 ctDNA-evaluable pts, detectability decreased from 96.7% at baseline to 48.9% preoperatively. Preoperative ctDNA positivity was significantly higher in Group A (78.6%) than in Group B (40.0%) and Group C (32.4%) (p<0.001). Importantly, on-treatment ctDNA status after cycle 1 was already associated with pathological response (p=0.0043). Pts with ctDNA clearance had higher pCR rates than those with persistent ctDNA (62.2% vs 9.1%, p<0.001). ctDNA clearance rates increased stepwise across pathological response categories: pCR (84.8%), MPR (48.1%), and non-responders (12.5%). Conclusion: Neoadjuvant CRT + S significantly improved pCR versus CT + S in RLA-ESCC. Preoperative ctDNA clearance status closely tracked pathological response, supporting ctDNA as a promising early molecular marker of treatment effect. EFS will be reported with longer follow-up. Clinical trial information: NCT05244798 . nCT + S nCRT + S nCRT pCR (95% CI) 18% (11, 26.9) 57.3% (47.2, 67) 49% (39.1, 59) P - value (vs. Group A) <0.0001 <0.0001 P - value (vs. Group B) 0.2942

How subduction evolution drives sediment-hosted mineralisation along craton edges

Abstract Sediment-hosted mineral deposits cluster near craton edges, yet the geodynamic factors influencing this concentration remain poorly understood. To investigate the tectonic and geodynamic controls on craton-edge mineralisation, we integrate a 1.8 Ga global plate motion model with craton-edge mapping from full-waveform seismic tomography, geodynamic modelling, and a global mineral deposit database. Here we show that mineralised craton edges consistently cluster 800–1800 km from subduction zones at the time of formation, with some as far away as ~3000 km—a spatial pattern distinct from random craton-edge locations. Geodynamic models show that subduction generates broad mantle return-flow cells that focus lithospheric stress, strain, and weakening at comparable distances from the trench. We propose that this mechanically driven weakening promotes rifting, enhances permeability, and facilitates the infiltration of slab-derived volatiles, thereby preconditioning the lithosphere for metallogenesis. These results identify subduction–craton coupling as a first-order control on sediment-hosted mineral systems across multiple supercontinent cycles and provide a predictive geodynamic framework for understanding the distribution of continental resources through deep time.Subduction near cratons fosters conditions that enrich the mantle and promote mineral formation along craton edges.

Chiral Phosphoric Acid Catalyzed Asymmetric Ring Contraction of Isoxazoles under Dye-Free Photodriven Conditions