Combination of GT90001 and nivolumab in patients with advanced hepatocellular carcinoma: a multicenter, single-arm, phase 1b/2 study.

BACKGROUND: GT90001 (also known as PF-03446962) is an anti-ALK-1 monoclonal antibody and has shown activity in hepatocellular carcinoma (HCC). This phase 1b/2 study was designed to determine the recommended phase 2 dose (RP2D) of GT90001 plus nivolumab, and assess the safety and anti-tumor activity in patients with advanced HCC. METHODS: Patients with advanced HCC were recruited from 3 centers. Eligible patients in the dose de-escalation stage received the GT90001 on day 1 of a 14-day cycle in a rolling-six design with a fixed dose of nivolumab (3.0 mg/kg). Patients in dose-expansion stage received the RP2D of GT90001 plus nivolumab. Primary endpoint was safety. Key secondary endpoint was objective response rate (ORR) as per RECIST 1.1. RESULTS: Between July 9, 2019, and August 8, 2022, 20 patients were treated (6 in phase 1b; 14 in phase 2) and evaluable for analysis. In phase 1b, no dose-limiting toxicities were observed, and GT90001 7.0 mg/kg was confirmed as the RP2D. Common grade 3/4 adverse events (AEs) were platelet count decreased (15%). No deaths due to AEs were reported. Confirmed ORR and disease control rate were 30% (95% CI, 14.6%-51.9%) and 40% (95% CI, 21.9%-61.3%), respectively. Median duration of response was not calculated (95% CI, 7.39 months to not calculated). Median progression-free survival (PFS) was 2.81 months (95% CI, 1.71-9.33), with 6-month and 12-month PFS rates of 35% and 25%, respectively. One patient with multiple intra- and extra-hepatic metastases was diagnosed with pseudo-progression upon GT90001 plus nivolumab exposure. CONCLUSIONS: GT90001 plus nivolumab has a manageable safety profile and promising anti-tumor activity in patients with advanced HCC. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT03893695.

Secondary Amplifier Sampling Component Design of an X-ray Framing Detector Based on a Streak Tube.

The development of inertial confinement fusion (ICF) experiments necessitates the diagnostic instrument to have multiple frames with a high spatial and temporal resolution for the two-dimensional detection of the hot spot at the implosion end of the ICF. The existing sampling two-dimensional imaging technology in the world has superior performance; however, its subsequent development requires a streak tube with large lateral magnification. In this work, an electron beam separation device was designed and developed for the first time. The device can be used without changing the structure of the streak tube. It can be combined directly with the corresponding device and matched with a special control circuit. Based on the original transverse magnification, 1.77 times the secondary amplification can be achieved, which is conducive to expanding the recording range of the technology. The experimental results showed that the static spatial resolution of the streak tube after the inclusion of the device can still reach 10 lp/mm.

Multiple organ dysfunction and rhabdomyolysis associated with moonwort poisoning: Report of four cases.

BACKGROUND: Moonwort is a widely used Chinese herbal medicine. It has various pharmacological effects, such as relieving cough and preventing asthma. To date, multiple organ dysfunction and rhabdomyolysis caused by moonwort poisoning have not been reported. CASE SUMMARY: Here we report four cases of moonwort poisoning that presented with multiple organ dysfunction and rhabdomyolysis accompanied by vomiting, fatigue, and muscle aches. One patient was an adult male, two were adult females, and one was a boy, with an age range of 7-64 years. The adults were treated with hemoperfusion and symptomatic therapies, while the child was treated with plasma exchange and symptomatic therapies. All four patients recovered. CONCLUSION: Blood purification combined with symptomatic treatment may be an effective method for managing multiple organ dysfunction and rhabdomyolysis caused by acute moonwort poisoning.