Dose Finding Study of BI 836880 in Patients With Solid Tumors

A First-in Human Phase I, Non-randomised, Open-label, Multi-center Dose Escalation Trial of BI 836880 Administered by Repeated Intravenous Infusions in Patients With Solid Tumors.

This is a Phase I, non-randomized, uncontrolled, open-label, dose escalating study of BI 836880 administered intravenously. The eligible patient population will be patients with advanced solid tumours. At any time during the trial, it will not be permitted to escalate to a dose which does not fulfil the escalation with overdose control (EWOC) criterion

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BI 836880

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75248
    • INS Curie
• Germany
  • Augsburg, Germany, 86156
    • Universitätsklinikum Augsburg
  • Freiburg im Breisgau, Germany, 79106
    • Universitätsklinikum Freiburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Age >= 18 years
• Histologically or cytologically confirmed malignancy which is locally advanced or metastatic solid tumor, and either refractory after standard therapy for the disease or for which standard therapy is not reliably effective, e.g. they do not tolerate or have contraindications to otherwise available standard therapy and tumour lesions evaluable for Dynamic contrast-enhanced (DCE)-MRI at MTD.
• ECOG performance status <= 2
• Adequate hepatic, renal and bone marrow functions
• Signed written informed consent.
• Life expectancy min. 3 months in the opinion of the investigator
• Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or CTCAE grade 1, except for alopecia (any grade) sensory peripheral neuropathy CTCAE grade <= 2 or considered not clinically significant.
• adequate contraception by male and female patient during the trial and for at least 6 months after end of treatment.

Exclusion criteria:

• Known hypersensitivity to the trial drugs or their excipients
• Current or prior treatment with any systemic anti-cancer therapy either within 28 days or a minimum of 5 half-lives, whichever is shorter of trial onset.
• Serious concomitant disease, especially those affecting compliance with trial requirements or which are considered relevant for the evaluation of the endpoints of the trial drug
• Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment, or planned surgical procedures during the trial period.
• patients with personal or family history of QT prolongation and/or long QT syndrome, or prolonged QTcF at baseline (> 470 ms). QTcF will be calculated by Investigator as the mean of the 3 ECGs taken at screening.
• Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure > NYHA II). Uncontrolled hypertension defined as: blood pressure in rested and relaxed condition >=140 mmHg systolic, or >=90 mmHg diastolic (with or without medication), measured according to protocol.
• History of severe haemorrhagic or thromboembolic event in the past 12 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis).
• Known inherited predisposition to bleeding or to thrombosis in the opinion of the investigator.
• Patient with brain metastases that are symptomatic and/or require therapy.
• Patients who require full-dose anticoagulation (according to local guidelines).
• Active alcohol or drug abuse in the opinion of the investigator.
• Patients who are under judicial protection and patients who are legally institutionalized.
• Patients unable or unwilling to comply with protocol
• Women who are pregnant, nursing, or who plan to become pregnant while in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 40 mg BI 836880; BI 836880	Drug: BI 836880; BI 836880
Experimental: 120 mg BI 836880; BI 836880	Drug: BI 836880; BI 836880
Experimental: 360 mg BI 836880; BI 836880	Drug: BI 836880; BI 836880
Experimental: 720 mg BI 836880; BI 836880	Drug: BI 836880; BI 836880
Experimental: 1000 mg BI 836880; BI 836880	Drug: BI 836880; BI 836880

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	Maximum tolerated dose (MTD) defined as the highest dose with less than 25% risk of the true dose-limiting toxicity (DLT) rate being above 0.33 during the MTD evaluation period, defined as 3 weeks after first administration of trial medication (i.e. cycle 1). Patients who did not complete the MTD evaluation period for reasons other than DLT were excluded from the analysis of the primary endpoint.	Up to 3 weeks after the first administration of trial medication.
Number of Patients With Dose-limiting Toxicities (DLT) in the Maximum Tolerated Dose (MTD) Period	DTLs are defined as followed: Drug-related Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 non-haematological toxicity; CTCAE Grade 4 neutropenia lasting >7 days or complicated by infection (please note that in case of grade 4 neutropenia a more frequent follow up of patient was necessary; Febrile neutropenia of CTCAE Grade ≥3; CTCAE Grade 4 thrombocytopenia or CTCAE Grade ≥3 thrombocytopenia with bleeding; Treatment delay for >2 weeks due to unresolved drug-related AEs, which started within 3 weeks after the first treatment; Hypertension: increase of diastolic blood pressure (DBP) by 15 millimetre of mercury (mmHg) confirmed by a second measurement or by ambulatory blood pressure measurement (when indicated, e.g. white coat effect) which could not be controlled by hypertensive medication and required a dose reduction of BI 836880 for further treatment cycle; Proteinuria: urinary protein ≥3.5 gram/day (CTCAE Grade 3)	Up to 3 weeks after the first administration of trial medication.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Drug-related Adverse Events Leading to Dose Reduction or Discontinuation During Treatment Period	Number of patients with drug-related adverse events leading to dose reduction or discontinuation during treatment period.	From first drug infusion until 42 days (residual effect period) after last drug infusion, up to 828 days.
Area Under the Serum Concentration-time Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC0-tz) After the First Dose	Area under the serum concentration-time curve over the time interval from 0 extrapolated to infinity (AUC0-tz) after the first dose.	5 minutes before start of BI 836880 infusion and immediately after end of infusion (i.e. 1.5 hours (h) after start of infusion) and 2h, 3h, 5h, 8h, 24h, 72h, 168h, 336h and 504h after start of BI 826880 infusion in cycle 1.
Terminal Half-life (t_1/2) of BI 836880	Terminal half-life (t_1/2) of BI 836880.	5 minutes before start of BI 836880 infusion and immediately after end of infusion (i.e. 1.5 hours (h) after start of infusion) and 2h, 3h, 5h, 8h, 24h, 72h, 168h, 336h and 504h after start of BI 826880 infusion in cycle 1.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

General Publications

• Le Tourneau C, Becker H, Claus R, Elez E, Ricci F, Fritsch R, Silber Y, Hennequin A, Tabernero J, Jayadeva G, Luedtke D, He M, Isambert N. Two phase I studies of BI 836880, a vascular endothelial growth factor/angiopoietin-2 inhibitor, administered once every 3 weeks or once weekly in patients with advanced solid tumors. ESMO Open. 2022 Oct;7(5):100576. doi: 10.1016/j.esmoop.2022.100576. Epub 2022 Sep 13.
• Keller S, Kunz U, Schmid U, Beusmans J, Buchert M, He M, Jayadeva G, Le Tourneau C, Luedtke D, Niessen HG, Oum'hamed Z, Pleiner S, Wang X, Graeser R. Comprehensive biomarker and modeling approach to support dose finding for BI 836880, a VEGF/Ang-2 inhibitor. J Transl Med. 2024 Oct 14;22(1):934. doi: 10.1186/s12967-024-05612-x.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2016
• Primary Completion (Actual): September 12, 2018
• Study Completion (Actual): November 4, 2020

Study Registration Dates

• First Submitted: January 4, 2016
• First Submitted That Met QC Criteria: February 2, 2016
• First Posted (Estimated): February 4, 2016

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 1336.1; 2014-005395-28 (EudraCT Number)