Yan Ma

PURPOSE: Trastuzumab deruxtecan (T-DXd) is a human epidermal growth factor 2 (HER2)-directed antibody-drug conjugate approved in HER2-expressing breast and gastric cancers and HER2-mutant non-small-cell lung cancer. Treatments are limited for other HER2-expressing solid tumors. METHODS: This open-label phase II study evaluated T-DXd (5.4 mg/kg once every 3 weeks) for HER2-expressing (immunohistochemistry [IHC] 3+/2+ by local or central testing) locally advanced or metastatic disease after ≥1 systemic treatment or without alternative treatments. The primary end point was investigator-assessed confirmed objective response rate (ORR). Secondary end points included safety, duration of response, progression-free survival (PFS), and overall survival (OS). RESULTS: At primary analysis, 267 patients received treatment across seven tumor cohorts: endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, and other. The median follow-up was 12.75 months. In all patients, the ORR was 37.1% (n = 99; [95% CI, 31.3 to 43.2]), with responses in all cohorts; the median DOR was 11.3 months (95% CI, 9.6 to 17.8); the median PFS was 6.9 months (95% CI, 5.6 to 8.0); and the median OS was 13.4 months (95% CI, 11.9 to 15.5). In patients with central HER2 IHC 3+ expression (n = 75), the ORR was 61.3% (95% CI, 49.4 to 72.4), the median DOR was 22.1 months (95% CI, 9.6 to not reached), the median PFS was 11.9 months (95% CI, 8.2 to 13.0), and the median OS was 21.1 months (95% CI, 15.3 to 29.6). Grade ≥3 drug-related adverse events were observed in 40.8% of patients; 10.5% experienced adjudicated drug-related interstitial lung disease (ILD), with three deaths. CONCLUSION: Our study demonstrates durable clinical benefit, meaningful survival outcomes, and safety consistent with the known profile (including ILD) in pretreated patients with HER2-expressing tumors receiving T-DXd. Greatest benefit was observed for the IHC 3+ population. These data support the potential role of T-DXd as a tumor-agnostic therapy for patients with HER2-expressing solid tumors.

Black carbon (BC), brown carbon (BrC), and mineral dust (DU) are three major light absorbing aerosols, playing important roles in climate change. Better knowledge of their concentrations is necessary for more accurate estimates of their radiative forcing effects of climate. We present a method to retrieve columnar contents of BC, BrC, and DU simultaneously from spectral refractive indices and spectral single scattering albedo obtained from the sun‐sky radiometer measurements. Then, this method is applied to investigate the columnar volume fractions and mass concentrations of BC, BrC, and DU in Beijing, China, based on measurements obtained from 2009 to 2010. Results show that among the three absorbing aerosols, DU dominates the largest volume fraction in the total aerosol volume (20–45%), followed by BrC (5–25%), and BC (< 5%). The retrieved monthly mean content of each absorbing component exhibits clear seasonal variation. BrC dominates in late fall and winter (40–92.5 mg/m 2 ), whereas is extremely low in summer (< 10 mg/m 2 ). DU dominates in spring, ranging from 270 to 405 mg/m 2 (with volume fraction >30%), while during June–September, the DU fraction is generally lower than 30%. BC is characterized by low levels throughout the year. The monthly mean BC columnar mass concentration ([BC]) ranges from 2.7 to 7.3 mg/m 2 with winter slightly higher than other seasons. As a preliminary validation, we compare our retrieved [BC] with in situ measurements. Similar day‐to‐day variation trends and good correlations are found between the retrieved [BC] and in situ measurements.

LBA3000 Background: T-DXd is an antibody drug conjugate targeting HER2 and is approved in HER2-expressing breast (BC) and gastric (GC) cancers. HER2 expression is prevalent in other solid tumors. The efficacy of current treatments (Tx) in these populations, including studies with HER2-directed Tx, is modest, revealing a significant unmet medical need. Clinically meaningful activity of T-DXd was seen in HER2-expressing tumors in a phase 1 study (NCT02564900). Methods: DP-02 (NCT04482309) is an open-label phase 2 study of T-DXd 5.4 mg/kg q3w in pts with HER2-expressing (immunohistochemistry [IHC] 3+ or IHC 2+ by local or central testing) locally advanced or metastatic disease that progressed after ≥1 systemic Tx or that has no Tx options. Cohorts with biliary tract (BTC), bladder (URO), cervical (CC), endometrial (EC), ovarian (OC), pancreatic (PC), or other tumors (excluding BC, GC, colorectal cancer, and non-small cell lung cancer) were enrolled. Efficacy and safety were analyzed in all pts who received ≥1 dose of T-DXd. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR), disease control rate, progression-free and overall survival, and safety. Results: At data cutoff (16 Nov 2022; median follow-up, 9.7 mo), 267 pts had been treated (median, 2 prior lines of Tx [range, 0-13]); 75 pts were IHC 3+ and 125 were IHC 2+ by central testing. In all 267 pts, the ORR was 37.1% and median DOR (mDOR) was 11.8 mo; in pts with IHC 3+ expression, the ORR was 61.3% and mDOR was 22.1 mo. ORR per cohort is shown in all pts and those with centrally confirmed HER2 IHC 3+ or IHC 2+ expression. Grade (G) ≥3 adverse events (AEs) occurred in 58.4% of pts; 11.6% discontinued Tx due to AEs. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 18 pts (6.7% [G1, n=6; G2, n=11; G5, n=1]). Conclusions: This is the first tumor-agnostic global study of T-DXd in a broad range of HER2-expressing solid tumors. T-DXd showed encouraging ORR, particularly in pts with IHC 3+ expression, durable clinical benefit, and a manageable safety profile in this heavily pretreated population. These interim results show T-DXd to be a potential new Tx option for pts with HER2-expressing solid tumors. Clinical trial information: NCT04482309 . [Table: see text]

This report describes the genetic characterization of 297 wild-type measles viruses that were isolated in 24 provinces of China between 1995 and 2003. Phylogenetic analysis of the N gene sequences showed that all of the isolates belonged to genotype H1 except 3 isolates, which were genotype A. The nucleotide sequence and predicted amino acid homologies of the 294-genotype H1 strains were 94.7%-100% and 93.3%-100%, respectively. The genotype H1 isolates were divided into 2 clusters, which differed by approximately 2.9% at the nucleotide level. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Even though other measles genotypes have been detected in countries that border China, this report shows that genotype H1 is widely distributed throughout the country and that China has a single, endemic genotype. This important baseline data will help to monitor the progress of measles control in China.

As the successors of the overdue HuanjingJianzai-1 (HJ-1) satellites and new members in Chinese Environmental Protection and Disaster Monitoring Satellite Constellation, the first two of HuanjingJianZai-2 series satellites (HJ-2 A/B) have been launched on September 27, 2020. Each satellite carries four sensors, including the Polarized Scanning Atmospheric Corrector (PSAC), the charge-coupled device (CCD) camera, the hyperspectral imager (HSI) and the infrared spectroradiometer (IRS). Among them, PSAC is mainly used for the monitoring of atmospheric parameters to provide data support for atmospheric environmental monitoring and atmospheric correction of data from other sensors. To test the in-orbit performance of PSAC, we develop the “day-1” aerosol and water vapor retrieval algorithms. The preliminary validation results based on ground-based observations show that the aerosol optical depth (AOD) and columnar water vapor (CWV) datasets developed based on PSAC data have high accuracy and can effectively characterize the temporal trends of AOD and CWV. The accuracy of PSAC AOD dataset is better than the expected error ±(0.05 + 0.2 * AODAERONET), and the accuracy of PSAC CWV dataset is better than the expected error ±(0.5 + 0.15 * CWVAERONET). To eliminate the negative impact of the atmosphere on CCD data and expand its application range, aerosol and water vapor data developed based on PSAC are used for atmospheric correction of CCD data. Compared with L1 CCD data, the texture details and clarity of CCD data after atmospheric correction have been significantly improved.