Subthalamic nucleus stimulation is emerging as an effective surgical therapy for Parkinson's disease. It is considered to be a safe procedure with little morbidity, the most common complications being intracranial haemorrhage and hardware failure. We report on three cases of depression, one of whom attempted suicide after bilateral subthalamic nucleus stimulation.
115 Background: BI 905711 is a tetravalent bispecific antibody that cross-links TRAILR2 with CDH17. This cross-linking drives CDH17-dependent TRAILR2 oligomerization, leading to caspase activation and eventual apoptosis, inhibiting tumor growth in preclinical models of GI cancer. Methods: This Phase Ia/b study of BI 905711 in patients (pts) with advanced GI cancers (NCT04137289) aimed to determine the maximum tolerated dose (MTD) based on the proportion of pts with dose-limiting toxicities (DLT) and explore preliminary antitumor activity. In Phase Ia, pts received BI 905711 every 14 days. One pt with colorectal cancer (CRC) was enrolled at each of the 2 lowest dose levels (0.02/0.06 mg/kg) and 4 pts with CRC were enrolled at each subsequent level (0.2/0.6/1.2/2.4/3.6/4.8 mg/kg). Up to 4 pts with non-CRC GI cancers were included at the dose level below the CRC cohort. Dose escalation was guided by a Bayesian logistic regression model. Results: As of 01 August 2022, 48 pts (CRC: n = 26; non-CRC: n = 22, including 13 with pancreatic ductal adenocarcinoma [PDAC]) had received BI 905711 (dose range 0.02–4.8 mg/kg); pts had a median age of 61 years (range 27–78) and had received a median of 3 (range 1–11) prior lines of treatment. No DLTs were observed and the MTD was not reached. 41 pts had AEs (grade [G] 3–5: 14 pts; serious: 13 pts). 17 pts had treatment-related AEs (TRAEs); 4 TRAEs were G3: AST increased (2 pts), fatigue and ALT increased (1 pt each). 1 pt had serious TRAEs: G2 decreased appetite and G3 fatigue. 2 pts had G1/2 infusion-related reactions that resolved and did not prevent resumption of treatment. PD biomarker modulation on the level of plasma caspase-3/7 activity was most common at 0.6 mg/kg (4/7 pts) or 1.2 mg/kg (2/6 pts). 13 pts achieved stable disease (SD) and 8 pts were progression-free for ≥4 months (PFS4). In pts with CRC, 6 pts achieved SD and 3 had PFS4. Among non-CRC pts, 7 pts achieved SD (PDAC: n = 6) and 5 had PFS4 (PDAC: n = 4). Median duration of treatment was 30.5 days (range 15–246) overall and 71 days (range 15–211) in the 0.6 mg/kg group (n = 8, predicted therapeutic dose; of whom 3 pts had PFS4: CRC: n = 1/4 [all CDH17+]; non-CRC: n = 2/4). Conclusions: In heavily pretreated pts, BI 905711 was associated with a tolerable safety profile and early signs of disease control. BI 905711 will be further assessed in Phase Ib in 4 dose groups: 0.6/1.2/2.4 mg/kg every 14 days, and 0.6 mg/kg weekly. Clinical trial information: NCT04137289 .
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.