Safety and Clinical Activity of SHR7390 Monotherapy or Combined With Camrelizumab for Advanced Solid Tumor: Results From Two Phase I Trials.

BACKGROUND: SHR7390 is a novel, selective MEK1/2 inhibitor. Here, we report results from two phase I trials conducted to evaluate the tolerability, safety and antitumor activity of SHR7390 monotherapy for advanced solid tumors and SHR7390 plus camrelizumab for treatment-refractory advanced or metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Patients received SHR7390 alone or combined with fixed-dose camrelizumab (200 mg every 2 weeks) in an accelerated titration scheme to determine the maximum tolerated dose (MTD). A recommended dose for expansion was determined based on the safety and tolerability of the dose-escalation stage. The primary endpoints were dose limiting toxicity (DLT) and MTD. RESULTS: In the SHR7390 monotherapy trial, 16 patients were enrolled. DLTs were reported in the 1.0 mg cohort, and the MTD was 0.75 mg. Grade ≥3 treatment-related adverse events (TRAEs) were recorded in 4 patients (25.0%). No patients achieved objective response. In the SHR7390 combination trial, 22 patients with CRC were enrolled. One DLT was reported in the 0.5 mg cohort and the MTD was not reached. Grade ≥3 TRAEs were observed in 8 patients (36.4%), with the most common being rash (n=4). One grade 5 TRAE (increased intracranial pressure) occurred. Five patients (22.7%) achieved partial response, including one of 3 patients with MSS/MSI-L and BRAF mutant tumors, one of 15 patients with MSS/MSI-L and BRAF wild type tumors, and all 3 patients with MSI-H tumors. CONCLUSIONS: SHR7390 0.5 mg plus camrelizumab showed a manageable safety profile. Preliminary clinical activity was reported regardless of MSI and BRAF status.

Investigation of mean glandular dose in diagnostic mammography in China.

A survey of 420 exposures of mammography was performed with the parameters recorded. Entrance skin air kerma (ESAK) was measured and the mean glandular dose (MGD) was calculated according to the Dance's formula. Correlation analysis showed that several factors could affect the MGD level. Mann-whitney test and Non-parametric ANOVA analyses were used to compare the MGD level grouped by view type and radiographic systems. No significant difference was found in MGD between the craniocaudal (CC) group and the mediolateral oblique (MLO) group. The MGD level was higher in the CR group than in the other two groups. MGD was positively correlated with the compressed breast thickness (CBT). MGD varied with the half value layer (HVL) and increased first then decreased. The mean MGD level in China is about 1.6 mGy and is lower than the guidance level in the International Basic Safety Standards (IBSS).