A Study to Test Different Doses of BI 1810631 in People With Different Types of Advanced Cancer (Solid Tumours With Changes in the HER2 Gene)

Inclusion Criteria:

Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic non-haematologic malignancy. Patient must show presence of at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Eastern Cooperative Oncology Group score of 0 or 1.
Availability and patient willingness to provide a sample of tumour for confirmation of the patient´s Human epidermal growth factor receptor 2 (HER2) status. This sample can be archival material obtained at any time prior to study enrollment.
Patient willing and able to comply with the protocol requirements for tumour biopsies (biopsies from brain metastases are not allowed).

Adequate organ function defined as all of the following:

Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (≥ 1.5 x 103/μL) (≥ 1500/mm3); haemoglobin ≥ 9.0 g/dL (≥ 90 g/L) (≥ 5.6 mmol/L); platelets ≥ 100 x 109/L (100 x 103/μL) (100 x 103/mm3) without the use of hematopoietic growth factors within 4 weeks of start of trial medication.
Total bilirubin ≤ 1.5 times 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.
Estimated Glomerular Filtration Rate (eGFR) ≥ 50 mL/min - calculated using Chronic Kidney Disease Epidemiology (CKD-EPI) formula.
Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN if no demonstrable liver metastases, or otherwise ≤ 5 x ULN if transaminase elevation is attributable to liver metastases.
Alkaline Phosphatase < 5 x ULN.
Recovered from any previous therapy-related toxicity to ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at start of treatment (except for alopecia, stable sensory neuropathy and hypothyroidism (patients on thyroid replacement therapy) which must be ≤ CTCAE Grade 2)
Life expectancy of at least 12 weeks at the start of treatment in the opinion of the investigator.
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 Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
Male or female patients. Women of childbearing potential (WOCBP)1 and men who are able to father a child must be ready and able to use highly effective methods of birth control per International Council on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly.

Additional inclusion criteria for Phase Ia

Patients with a documented diagnosis of HER2 aberration: overexpression OR gene amplification OR non-synonymous somatic mutation OR gene rearrangement involving HER2 or Neuregulin 1 (NRG1)
Patient who has failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options. Patient must have exhausted, or not be a suitable candidate for, available treatment options known to prolong survival for their disease

Additional inclusion criteria for Phase Ib - Cohort 1 only

Non-small cell lung cancer (NSCLC) patients with documented human epidermal growth factor receptor 2 (HER2) mutation.
Patient who had received, in the advanced/metastatic setting, at least one line of systemic therapy. Patients with NSCLC harboring additionally genomic aberrations for which approved targeted therapy is available as standard of care.

Additional inclusion criteria for Phase Ib - Cohort 2 only

NSCLC Patient with a documented HER2 mutation.
Treatment naïve for NSCLC.

Additional inclusion criteria for Phase Ib - Cohort 3 only

NSCLC Patient with a documented HER2 mutation.
Patient who had received, in the advanced/metastatic setting, at least one line of systemic therapy. Patients with NSCLC harboring additionally genomic aberrations for which approved targeted therapy is available as standard of care.

Exclusion Criteria:

Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to first trial treatment or planned within 6 months after screening

Previous or concomitant malignancies other than the one treated in this trial within the last 2 years, except;

effectively treated non-melanoma skin cancers
effectively treated carcinoma in situ of the cervix
effectively treated ductal carcinoma in situ
other effectively treated malignancy that is considered cured by local treatment.
Treatment with a systemic anti-cancer therapy or investigational drug within 21 days or 5 half-lives (whichever is shorter) of the first treatment with the study medication
Patients who must or wish to continue the intake of restricted medication or any drug considered likely to interfere with the safe conduct of the trial
Use of concomitant medications that are narrow therapeutic index drugs that are substrates of P-Glycoprotein (P-gp) or Breast Cancer Resistance Protein (BCRP) (e.g. digoxin, dabigatran etexilate)
Treatment with strong Cytochrome P450 3A4 (CYP3A4) inhibitors
Treatment with strong Cytochrome P450 3A (CYP3A) inducers
Treatment with Proton Pump Inhibitors (PPIs) or Potassium-competitive acid blockers (PCAB). Patients on these therapies may switch to antiacid or H2antagonists at the discretion of the investigator.

Further exclusion criteria apply