A Trial to Find the Safe Dose for BI 905681 in Patients With Incurable Tumours or Tumours That Have Spread

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

The primary objective of this trial is to determine the maximum tolerated dose (MTD)/optimal biological dose (OBD) of BI 905681 given as an intravenous infusion and to determine the recommended dose and dosing schedule for further trials in the development of BI 905681. The MTD will be defined based on the frequency of patients experiencing dose-limiting toxicities (DLTs) during the MTD/DLT evaluation period, which is defined as the first cycle of treatment. Separate MTDs will be determined for Schedule A and Schedule B.

The secondary objective of the trial is to determine the pharmacokinetic (PK) profile of BI 905681.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BI 905681

Detailed Description

Study was opened to recruitment until 29-Oct-2021, however from 15-Apr-2021 no patient was recruited.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

• Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic non-haematologic malignancy. Patient must have measurable or evaluable lesions (according to Response Evaluation Criteria in Solid Tumours (RECIST) v 1.1).
• Patient who has failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options.
• Patients willing to undergo mandatory tumour biopsy at the time points specified in the protocol.
• Eastern Cooperative Oncology Group (ECOG) Score of 0 or 1 (R01-0787).

• Adequate organ function defined as all of the following:

  • Absolute neutrophil count (ANC) ≥1.5 x 10^9/L; haemoglobin ≥9.0 g/dL; platelets ≥100 x 10^9/L without the use of haematopoietic growth factors within 4 weeks of start of study medication.
  • Total bilirubin ≤1.5 x the upper limit of normal (ULN), except for patients with Gilbert's syndrome: total bilirubin ≤3 x ULN or direct bilirubin ≤1.5 x ULN.
  • Creatinine ≤1.5 x ULN. If creatinine is >1.5 x ULN, patient is eligible if concurrent creatinine clearance ≥50 ml/min (measured or calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula or Japanese version of CKD-EPI formula for Japanese patients).
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 x ULN if no demonstrable liver metastases, or otherwise ≤5 x ULN
  • Alkaline Phosphatase (ALP) <5 x ULN
• At least 18 years of age at the time of consent or over the legal age of consent in countries where that is greater than 18 years.
• Signed and dated written informed consent in accordance with International Conference on Harmonisation (ICH) - Good Clinical Practice (GCP) and local legislation prior to admission to the trial
• Life expectancy ≥3 months at the start of treatment in the opinion of the investigator
• Further inclusion criteria apply

Exclusion criteria:

• Osteoporosis ≥ CTCAE Grade 2
• Osteoporotic compression fracture within 12 months prior to informed consent which is clinically significant in the opinion of the investigator.
• Further exclusion criteria apply

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: 1.0 milligram/kilogram BI 905681; Subjects received an intravenous infusion of 1.0 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.	Drug: BI 905681; Infusion
Experimental: 2.5 milligram/kilogram BI 905681; Subjects received an intravenous infusion of 2.5 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.	Drug: BI 905681; Infusion
Experimental: 5.0 milligram/kilogram BI 905681; Subjects received an intravenous infusion of 5.0 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.	Drug: BI 905681; Infusion
Experimental: 7.0 milligram/kilogram BI 905681; Subjects received an intravenous infusion of 7.0 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.	Drug: BI 905681; Infusion
Experimental: 8.5 milligram/kilogram BI 905681; Subjects received an intravenous infusion of 8.5 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.	Drug: BI 905681; Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Maximum Tolerated Dose (MTD)/Optimal Biological Dose (OBD) of BI 905681	The MTD/OBD of BI 905681. The MTD will be assessed based on the number of patients experiencing Dose Limiting Toxicities (DLTs), graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, in the first cycle of treatment (3 weeks). The MTD is defined as the highest dose with less than 25% risk of the true DLT rate being equal to or above 33%.	The first cycle of treatment, up to 21 days.
Number of Patients Experiencing Adverse Events (AEs) During the Entire Treatment Period	Number of patients experiencing adverse events (AEs) during the entire treatment period.	From the first administration of study till the last administration of study drug +42 days, up to 126 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax: Maximum Measured Concentration of BI 905681 in Serum After First Infusion	Cmax: maximum measured concentration of BI 905681 in serum after first infusion.	5 minutes before and 1, 1.5, 4, 8, 24, 72, 168, 336 and 504 (5 minutes before 2nd infusion) hours following the first infusion.
AUC0-tz: Area Under the Serum Concentration-time Curve Over the Time Interval From 0 to the Last Measured Time Point (tz)	AUC0-tz: area under the serum concentration-time curve over the time interval from 0 to the last measured time point (tz).	5 minutes before and 1, 1.5, 4, 8, 24, 72, 168, 336 and 504 (5 minutes before 2nd infusion) hours following the first infusion.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2019
• Primary Completion (Actual): May 6, 2021
• Study Completion (Actual): May 27, 2021

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: October 30, 2019
• First Posted (Actual): November 1, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 1424-0001; 2019-003490-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No