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Endocrinology and Metabolic Disease

Small molecule drug

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Disease Domain	Count

Endocrinology and Metabolic Disease	1

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Small molecule drug	1

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SUR(Sulfonylurea receptor)	1

PURPOSEThis phase Ib study investigated the safety and antitumor activity of BI 836880, a bispecific nanobody targeting vascular endothelial growth factor and angiopoietin-2, and ezabenlimab, an anti–PD-1 antibody, in patients with advanced or metastatic solid tumors.METHODS This was an open-label, multinational study (ClinicalTrials.gov identifier: NCT03468426 ) conducted in two parts. Part 1 was a dose-escalation phase to determine the recommended phase II dose (RP2D) of BI 836880 in combination with ezabenlimab in patients with metastatic non–small cell lung cancer (mNSCLC). Part 2 was an expansion phase investigating the efficacy and safety of the combination at the RP2D in eight cohorts, on the basis of tumor type. The primary end point of part 2 was objective response rate (ORR). RESULTSOverall, 14 patients were recruited in part 1 and 238 in part 2. In part 1, the maximum tolerated dose of the combination was not reached; the RP2D was BI 836880 720 mg plus ezabenlimab 240 mg every 3 weeks. In part 2, the ORR was 18.9% across all cohorts. In the mNSCLC cohorts, ORRs were 16.7% (after checkpoint inhibitor [CPI] monotherapy) and 7.5% (after chemotherapy + CPI). Notably higher rates were seen in patients with glioblastoma (GBM; 22.6%); hepatocellular carcinoma (HCC) who had previously received sorafenib or lenvatinib (40.0%); and previously untreated HCC (25.8%). The combination was well tolerated; the most common adverse events in part 2 were asthenia (27.3%), hypertension (21.4%), and diarrhea (20.2%).CONCLUSIONBI 836880 combined with ezabenlimab had a positive benefit-risk ratio, with a manageable safety profile and signs of antitumor activity across a wide range of tumor types, with particularly promising activity in patients with HCC and GBM.

01 Nov 2024·ESMO Open

A phase I dose-escalation study of LRP5/6 antagonist BI 905677 in patients with advanced solid tumors

Article

Author: Argilés, G ; Doi, T ; Kuboki, Y ; de Jonge, M J A ; El-Khoueiry, A ; Yaeger, R ; Tabernero, J ; Bertulis, J ; Lenz, H-J ; Nazabadioko, S ; Eskens, F ; Pronk, L

BACKGROUNDAberrant Wnt pathway signaling has been implicated in the development of many cancers. Targeting of low-density lipoprotein receptor-related protein 5/6 (LRP5/6) co-receptors inhibits Wnt signaling and may be a novel therapy. BI 905677 is an LRP5/6 antagonist that has demonstrated preclinical antitumor activity.PATIENTS AND METHODSThis (NCT03604445) was a phase I, dose-escalation study evaluating BI 905677 for patients with advanced solid tumors over two dosing schedules (A: i.v. infusion every 3 weeks, 3-week cycles; B: i.v. infusion every 2 weeks, 4-week cycles). Adult patients were eligible if they had exhausted treatment options and had an Eastern Cooperative Oncology Group performance status of 0-1. The primary endpoints were the maximum tolerated dose (MTD) and safety. Other endpoints were pharmacokinetics, pharmacodynamics, and efficacy.RESULTSIn total, 37 patients received BI 905677 over nine dose cohorts (0.05-3.6 mg/kg/every 3 weeks). Dose-limiting toxicities were only reported during cycle 1 in the 3.6 mg/kg cohort and the MTD was established at 2.8 mg/kg every 3 weeks. Enrollment for schedule B was not pursued. The most frequently reported adverse events were diarrhea (35.1%), vomiting (21.6%), and C-telopeptide increase (18.9%). All patients in the 3.6 mg/kg cohort experienced a dose-limiting toxicity, suggesting a narrow therapeutic index. Paired pre-treatment and on-treatment biopsies, where available, showed decreased Axin2 expression by reverse transcriptase polymerase chain reaction with treatment, suggesting target inhibition. Best response observed was stable disease in 14 (38%) patients.CONCLUSIONThe MTD of BI 905677 was set at 2.8 mg/kg every 3 weeks. BI 905677 was well tolerated but a narrow therapeutic range and minimal efficacy led to early termination of the trial.

01 Nov 2024·ESMO Open

A phase I dose escalation study of the LRP5 antagonist BI 905681 in patients with advanced and metastatic solid tumors

Article

Author: Bashir, B ; Pronk, L ; Muskens, B ; Wang, J S ; Spigel, D R ; Burris, H ; Teufel, M

BACKGROUNDThe Wnt pathway is involved in proliferation and tissue homeostasis. Aberrant activation promotes cancer cell proliferation and survival. Inhibition of the low-density lipoprotein receptor-related protein 5/6 (LRP5/6) coreceptors that regulate Wnt signaling could prevent cancer cell proliferation. BI 905681 is a novel LRP5 antagonist that has demonstrated potent in vivo antitumor activity.PATIENTS AND METHODSThis was a phase I, dose escalation study (NCT04147247) evaluating BI 905681 in patients with advanced solid tumors over two dosing schedules (schedule A: every 3 weeks, 3-week cycles and schedule B: every 2 weeks, 4-week cycles). The primary endpoint was the maximum tolerated dose (MTD) of BI 905681 and the number of patients experiencing adverse events (AEs). Other endpoints were pharmacokinetics, pharmacodynamics, and efficacy.RESULTSAs a result of difficulties enrolling patients, the trial was terminated early and the MTD for schedule A could not be determined. Twenty-one patients received BI 905681 over five dose cohorts (schedule A: 1.0, 2.5, 5.0, 7.0, and 8.5 mg/kg). No patients received schedule B. No dose-limiting toxicities (DLTs) were reported during the MTD evaluation period. However, during the entire treatment period, two patients (9.5%) experienced a DLT of grade 1 C-telopeptide increase in the 5.0 and 8.5 mg/kg dose cohorts. The most frequent treatment-related AEs were diarrhea (23.8%), vomiting (23.8%), nausea (19.0%), and infusion-related reactions (IRRs; 14.3%). Despite premedication to mitigate IRRs, one patient experienced a grade 2 IRR. The pharmacokinetic profiles of BI 905681 were biphasic, with a rapid distribution phase in the beginning followed by a slower elimination phase. The objective response rate was 0%; 5 (23.8%) and 14 patients (66.7%) had a best overall response of stable disease and progressive disease, respectively.CONCLUSIONBI 905681 has minimal efficacy in an unselected patient population and was generally well tolerated.

100 Deals associated with Boehringer Ingelheim España SA

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100 Translational Medicine associated with Boehringer Ingelheim España SA

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Pipeline

Pipeline Snapshot as of 02 Feb 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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