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

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

Treated Set (TS): includes all patients who received at least one infusion of BI 905681.

From the first administration of study till the last administration of study drug +42 to 49 days, up to 133 days.

Treated Set (TS): includes all patients who received at least one infusion of BI 905681.

Trial was prematurely discontinued due to limited antitumor activity (i.e., lack of a single objective response) & difficulty in enrolling patients with RNF43 (Ring Finger Protein 43) mutations or R-spondin fusions who were willing to undergo a biopsy. The trial aimed to test two schedules for BI 905681 (A: every three weeks in a 3-week cycle, B: every 2 weeks in a 4-week cycle). Maximum tolerated dose/Recommended Phase 2 dose for Schedule A could not be determined, schedule B was not pursued.