Evidence map›Paper›PMID 39617535›Full record

ArticleESMO open2024

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

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

Registry-linked trialAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in ESMO open, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04147247 (An Open-label, Phase I Trial to Determine the Maximum-tolerated Dose and Investigate Safety, Pharmacokinetics and Efficacy of BI 905681 Administered Intravenously in Patients With Advanced Solid Tumours), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04147247 phase1completednot on this map

An Open-label, Phase I Trial to Determine the Maximum-tolerated Dose and Investigate Safety, Pharmacokinetics and Efficacy of BI 905681 Administered Intravenously in Patients With Advanced Solid Tumours

TypeinterventionalSponsorBoehringer IngelheimRan2019 to 2021Enrolled21ConditionsNeoplasmsArmsBI 905681
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Beyond the target: implications of Wnt pathway inhibitors on bone health.Journal of molecular medicine (Berlin, Germany) · 2026
    Review
  2. Review
  3. Mutanobactin-D, aInternational journal of molecular sciences · 2025
    Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

D R SpigelSarah Cannon Research Institute, Nashville.
J S WangFlorida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, USA.
L PronkBoehringer Ingelheim España S.A., Madrid, Spain.
B MuskensVenn Life Sciences ED, Breda, the Netherlands.
M TeufelBoehringer Ingelheim Pharmaceuticals Inc., Ridgefield.
B BashirDepartment of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, USA. Electronic address: babar.bashir@jefferson.edu.
H BurrisSarah Cannon Research Institute, Nashville.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Low Density Lipoprotein Receptor-Related Protein-5Maximum Tolerated DoseNeoplasmsAdultAgedAntineoplastic AgentsDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedAntineoplastic AgentsLow Density Lipoprotein Receptor-Related Protein-5LRP5 protein, humanclinical trialLRP5phase Isolid tumorWnt

Identifiers

PMID39617535
PMCPMC11670693

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.