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

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