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

Study Overview
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Brief Summary
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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.

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

Official Title
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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

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: BI 905681


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1.0 milligram/kilogram BI 905681<br>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<br>* Infusion<br>|
| Experimental: 2.5 milligram/kilogram BI 905681<br>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<br>* Infusion<br>|
| Experimental: 5.0 milligram/kilogram BI 905681<br>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<br>* Infusion<br>|
| Experimental: 7.0 milligram/kilogram BI 905681<br>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<br>* Infusion<br>|
| Experimental: 8.5 milligram/kilogram BI 905681<br>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<br>* Infusion<br>|

What is the study measuring?
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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. |