Efficacy and safety of serplulimab plus nab-paclitaxel in previously treated patients with PD-L1-positive advanced cervical cancer: a phase II, single-arm study.

Objective: We report the efficacy and safety of serplulimab, a novel humanized anti-programmed death-1 antibody, plus nanoparticle albumin-bound (nab)-paclitaxel in previously treated patients with programmed death ligand-1 (PD-L1)-positive advanced cervical cancer. Methods: Patients diagnosed with PD-L1-positive (combined positive score ≥1) cervical cancer were enrolled in this single-arm, open-label, phase II study. They were given serplulimab 4.5 mg/kg for up to 2 years (35 dosing cycles) plus nab-paclitaxel 260 mg/m2 for up to six cycles once every 3 weeks. Primary endpoints were safety and objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST version 1.1. Secondary endpoints included ORR assessed by the investigator, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Between December 2019 and June 2020, 52 patients were screened and 21 were enrolled. IRRC-assessed ORR was 57.1% (95% confidence interval [CI] 34.0-78.2%); 3 (14.3%) patients achieved complete response and 9 (42.9%) partial response. The median DOR was not reached (NR) (95% CI 4.1-NR). IRRC-assessed median PFS was 5.7 months (95% CI 3.0-NR), and median OS was 15.5 months (95% CI 10.5-NR). Investigator-assessed ORR was 47.6% (95% CI 25.7-70.2%). Seventeen (81.0%) patients experienced grade ≥3 treatment-emergent adverse events. Grade ≥3 adverse drug reactions were reported in 7 (33.3%) patients. Immune-related adverse events occurred in 12 (57.1%) patients. Conclusions: In previously treated patients with PD-L1-positive advanced cervical cancer, serplulimab plus nab-paclitaxel provided durable clinical activity and a manageable safety profile. Clinical trial registration: ClinicalTrials.gov, identifier NCT04150575.

Conjugated cross-linked phosphine as broadband light or sunlight-driven photocatalyst for large-scale atom transfer radical polymerization.

The use of light to regulate photocatalyzed reversible deactivation radical polymerization (RDRP) under mild conditions, especially driven by broadband light or sunlight directly, is highly desired. But the development of a suitable photocatalyzed polymerization system for large-scale production of polymers, especially block copolymers, has remained a big challenge. Herein, we report the development of a phosphine-based conjugated hypercrosslinked polymer (PPh3-CHCP) photocatalyst for an efficient large-scale photoinduced copper-catalyzed atom transfer radical polymerization (Cu-ATRP). Monomers including acrylates and methyl acrylates can achieve near-quantitative conversions under a wide range (450-940 nm) of radiations or sunlight directly. The photocatalyst could be easily recycled and reused. The sunlight-driven Cu-ATRP allowed the synthesis of homopolymers at 200 mL from various monomers, and monomer conversions approached 99% in clouds intermittency with good control over polydispersity. In addition, block copolymers at 400 mL scale can also be obtained, which demonstrates its great potential for industrial applications.

HLX22, an anti-HER-2 monoclonal antibody, in patients with advanced solid tumors overexpressing human epidermal growth factor receptor 2: an open-label, dose-escalation, phase 1 trial.

HLX22 is a novel monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2). This first-in-human, phase 1 dose-escalation study aimed to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HLX22 in patients with advanced solid tumors who had failed or were intolerant to standard therapies. Enrolled patients aged 18 to 75 years with histologically confirmed HER2-overexpressing advanced or metastatic solid tumors received intravenous HLX22 once every 3 weeks at 3, 10, and 25 mg/kg. Primary endpoints were safety and the maximum tolerated dose (MTD). Secondary endpoints included pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy. Between July 31, 2019, and December 27, 2021, 11 patients were enrolled to receive HLX22 at 3 (n = 5), 10 (n = 3), and 25 (n = 3) mg/kg doses. The most common treatment-emergent adverse events were lymphocyte count decreased (45.5%), white blood cell count decreased (36.4%), and hypokalemia (36.4%). No serious adverse events or dose-limiting toxicities occurred during the treatment period, and the MTD was determined at 25 mg/kg once every 3 weeks. Systemic exposure of HLX22 increased with escalating dose levels. No patients achieved a complete or partial response, and four (36.4%) had stable disease. The disease control rate and median progression-free survival were 36.4% (95% confidence interval [CI], 7.9-64.8) and 44.0 days (95% CI, 41.0-170.0), respectively. HLX22 was well tolerated in patients with advanced solid tumors overexpressing HER2 after failure of standard therapies. The study results support further investigation of HLX22 in combination with trastuzumab and chemotherapy.

Comparing the pharmacokinetics, safety, and immunogenicity of HLX02 to US- and EU-approved trastuzumab in healthy Chinese male subjects: A Phase I, randomized, double-blind, parallel-group study.

BACKGROUND: HLX02, the first China-manufactured trastuzumab biosimilar, is approved in Europe (EU) and China. This study evaluated bioequivalence between HLX02 and US-approved trastuzumab (US-trastuzumab). METHOD: In this double-blind, parallel-group, Phase I study, healthy Chinese men were randomized (1:1:1) to receive a single 6 mg/kg dose of HLX02, reference US-trastuzumab, or reference EU-approved trastuzumab (EU-trastuzumab). Equivalence in PK profiles was demonstrated if the 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for the difference between the least square means of the area under the curve (AUC) from time 0 to infinity (AUC∞) were 0.8-1.25. RESULTS: Pharmacokinetic profiles of the three trastuzumab products were similar in 111 Chinese men. Equivalence was confirmed between HLX02 and US-trastuzumab (GMR for AUC∞ 1.009, 90% CI 0.950-1.072); HLX02 and EU-trastuzumab (GMR for AUC∞ 1.068, 90% CI 1.005-1.135); and EU- and US-trastuzumab (GMR for AUC∞ 0.945, 90% CI 0.889-1004). Exploratory analysis of all other PK parameters also demonstrated equivalence between any two of the three trastuzumab products. HLX02 had similar safety and immunogenicity profiles to US- and EU-trastuzumab. CONCLUSION: HLX02 is bioequivalent to US-trastuzumab and EU-trastuzumab, with similar safety and immunogenicity profiles. US- and EU-trastuzumab were also bioequivalent to each other.

EDTA-enhanced alkaline anaerobic fermentation of landfill leachate-derived waste activated sludge for short-chain fatty acids production: Metals chelation and EPSs destruction.

Alkaline anaerobic fermentation (AAF) of waste activated sludge (WAS) has been demonstrated to be promising for short-chain fatty acids (SCFAs) recovery. However, high-strength metals and EPSs in the landfill leachate-derived WAS (LL-WAS) would stabilize its structure, suppressing AAF performance. To improve sludge solubilization and SCFAs production, AAF was coupled with EDTA addition for LL-WAS treatment. The results show that sludge solubilization at AAF-EDTA was promoted by 62.8% than AAF, releasing 21.8% more soluble COD. The maximal SCFAs production of 477.4 mg COD/g VSS was thus achieved, i.e., 1.21 and 6.13 times those at AAF and the control, respectively. SCFAs composition was also improved with more acetic and propionic acids (80.8% versus 64.3%). Metals bridging EPSs were chelated by EDTA, which significantly dissolved metals from sludge matrix (e.g., 23.28 times higher soluble Ca than AAF). EPSs tightly bound with microbial cells were thus destructed (e.g., 4.72 times more protein release than alkaline treatment), causing an easier sludge disruption and subsequently a higher SCFAs production by hydroxide ions. These findings suggest an effective EDTA-supported AAF for metals and EPSs-rich WAS to recover carbon source.

Quantifying Threshold Water Tables for Ecological Restoration in Arid Northwestern China.

In arid northwestern China, as many inland areas around the world with arid or semi-arid climate, inland river flow recharges groundwater; vegetation pattern depends on the water table, which characterizes the landscapes of oasis, transition zone and desert, within different distances from an inland river. The water table conditions play an important role in water and land management-a high water table causes salinization within the oasis while a low water table causes desertification around the oasis. This study applies a theoretical-empirical method to calculating critical groundwater depths including the depth of critical groundwater level causing salinization (DCGS) and the depth of critical groundwater level causing desertification (DCGD); the calculations are validated with field observations in the Luocheng Irrigation District located in the middle reach of the Heihe River, an inland river of the northwestern China. Specifically, the calculated DCGS is 1.29 m for the case study area and the range of water table depth at the locations with saline soil is 0.5-1.2 m. The calculated DCGD for three vegetation communities, Nitraria tangutorum + Glycyrrhiza uralensis Fisch community, Tamarix chinensis + Phragmites australis community, and Alhagi sparsifolia + Phragmites communis, are 8.26, 11.26, and 13.26 m, respectively, basically within an observed range of 6.0-13.0 m in the study area. The critical depths can be used to design an engineering approach to control water tables and mitigate salinization and desertification problem for ecosystem restoration in the study region.

An Effect Analysis of Comprehensive Treatment of Groundwater Over-Exploitation in Cheng'an County, Hebei Province, China.

The comprehensive treatment project of groundwater over-exploitation in Hebei Province has been implemented for more than a year, and the effect of exploitation restriction is in urgent need of evaluation. This paper deals with Cheng'an County of Hebei Province as the research subject. Based on collected hydro-meteorological, socioeconomic, groundwater, and other related data, together with typical regional experimental research, this study generates the effective precipitation-groundwater exploitation (P-W) curve and accompanying research methods, and calculates the quantity of groundwater exploitation restriction. It analyzes the target completion status of groundwater exploitation restriction through water conservancy measures and agricultural practices of the groundwater over-exploitation comprehensive treatment project that was implemented in Cheng'an County in 2014. The paper evaluates the treatment effect of groundwater over-exploitation, as well as provides technical support for the effect evaluation of groundwater exploitation restriction of agricultural irrigation in Cheng'an County and relevant areas.