A Phase I, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients with Advanced Gastrointestinal Stromal Tumor.

PURPOSE: To evaluate DS-6157a, an antibody-drug conjugate targeting G protein-coupled receptor 20 (GPR20), in gastrointestinal stromal tumors (GIST). PATIENTS AND METHODS: In this phase I multicenter, open-label, multiple-dose study, patients with previously treated advanced GIST received intravenous DS-6157a on Day 1 of 21-day cycles, with a starting dose of 1.6 mg/kg. The primary objective evaluated the safety and tolerability of DS-6157a, while determining dose-limiting toxicity (DLT) and the MTD. Secondary objectives included plasma pharmacokinetics parameters, plasma antidrug antibodies (ADA), and efficacy. RESULTS: A total of 34 patients enrolled. DS-6157a was well tolerated, with DLTs in 4 patients (11.8%) at doses of 6.4 mg/kg, 9.6 mg/kg, and 12.8 mg/kg; the MTD was determined to be 6.4 mg/kg. Treatment-emergent adverse events (TEAE) grade ≥3 occurred in 17 patients (50.0%), including decreased platelet count (23.5%), anemia (20.6%), decreased neutrophil count (14.7%), and decreased white blood cell count (11.8%). Four patients (11.8%) experienced serious adverse events related to DS-6157a. Six patients died with 5 due to disease progression and 1 due to DS-6157a-related TEAE. Tumor shrinkage was observed in 7 patients (20.6%), and 1 patient (2.9%) achieved a partial response. Plasma concentrations and exposure of intact DS-6157a, DXd, and total anti-GPR20 antibody all demonstrated a dose-dependent profile. No treatment-emergent ADAs were observed. CONCLUSIONS: Targeting GPR20 with DS-6157a was tolerated in patients with advanced GIST with tumor shrinkage demonstrated in KIT/PDGFRA wild-type GIST. However, the study did not proceed further due to lower efficacy outcomes than anticipated.

Differences in Glucose Readings Between Right Arm and Left Arm Using a Continuous Glucose Monitor.

OBJECTIVE: Continuous glucose monitoring (CGM) devices are used for evaluating real-time glucose levels to optimize diabetes management. There is limited information, however, on whether readings differ when a device is placed on the right versus the left arm. This study evaluated the mean difference in glucose levels between the right and left arm and the effect of unilateral arm exercise on this difference. The effect of an intermittent fasting diet on body fat percentage was also evaluated. RESEARCH DESIGN AND METHODS: In a prospective trial, 46 adult volunteers self-selected into the intermittent fasting (IF; N = 23) or free-living (FL; N = 23) diet group and were randomized into a unilateral arm exercise group. Volunteers had CGM sensors placed simultaneously on both arms for 12-14 days. RESULTS: The mean glucose level in the right arm was significantly higher than the left arm by 3.7 mg/dL (P < .001), and this result was unaffected by diet or arm exercise. Glucose levels were in euglycemic range for 75.2% of the time in the right arm and 67.5% in the left arm (P < .001). The change from baseline in body fat percentage between the IF and FL diet groups was not significant. CONCLUSIONS: Measured glucose level and time in euglycemic range differ per placement of the CGM device, and the implications of this difference should be considered in clinical practice and research.