A Study to Find a Safe and Effective Dose of BI 905711 in Patients With Advanced Gastrointestinal Cancer

Inclusion Criteria

• a. Phase Ia (dose escalation only)

Histologically or cytologically confirmed, advanced unresectable or metastatic gastrointestinal cancers of following histologies:

• Colorectal adenocarcinoma
• Gastric adenocarcinoma
• Esophageal adenocarcinoma
• Pancreatic adenocarcinoma
• Cholangiocarcinoma and gallbladder carcinoma
• Small intestine adenocarcinoma b. Phase Ib (expansion phase)
• Histologically or cytologically confirmed, advanced unresectable or metastatic colorectal adenocarcinoma.
• Patient who has failed all available conventional therapies known to confer clinical benefit for their disease based on local approved standards. For patients with colorectal cancer, prior treatment with regorafenib or TAS-102 is optional.
• Phase Ia (dose escalation) only: Patient with either measurable or non-measurable/non-evaluable disease.
• Phase Ia (expanded cohort) and Phase Ib (expansion phase) only: At least one target lesion that can be accurately measured per RECIST v.1.1
• Availability and willingness to provide an archived tumor tissue specimen and undergo tumor biopsy before treatment. Pre-treatment fresh tumor biopsy collections for biomarker analyses are considered optional in phase Ia and mandatory in phase Ib. Only nonsignificant risk procedures per the investigator's judgment will be used to obtain any biopsies specified in this study. In case a fresh tumor biopsy cannot be obtained due to before mentioned reasons an archived tumor tissue specimen obtained within ≤6 months of screening must be submitted. In case the patient undergoes baseline tumor biopsy, an archived tumor tissue specimen must be submitted regardless of the date of collection.
• Adequate hepatic, renal and bone marrow functions as defined by all of the below:
• Total bilirubin ≤ 1.5 x institutional Upper Level of Normal (ULN) (≤ 3 x institutional ULN for patient with Gilbert's syndrome)
• ALT and AST ≤2.5 x institutional ULN (≤5 x institutional ULN for patients with known liver metastases)
• Serum creatinine ≤1.5x institutional ULN. If creatinine is > 1.5 x ULN, patient is eligible if concurrent creatinine clearance ≥ 50 ml/min (>0.05 L/min) (measured or calculated by CKD-EPI formula or Japanese version of CKD-EPI formula for Japanese patients).
• ANC ≥ 1.0x 10^9/L (≥ 1.0 x 10^3/μL, ≥ 1,000/mm3)
• Platelets ≥ 100x10^9/ L (≥ 100 x 10^3/μL, ≥ 100 x 10^3/mm3)
• Hemoglobin (Hb) ≥8.5 g/dl, ≥ 85 g/L, or ≥ 5.3 mmol/L (without transfusion within previous week)
• Serum lipase ≤ 1.5 institutional ULN
• Recovery from any adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 of previous anti-cancer therapies to baseline or CTCAE grade 1, except for alopecia CTCAE grade 2, sensory peripheral neuropathy CTCAE grade ≤ 2 or considered not clinically significant.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Life expectancy ≥ 3 months in the opinion of the investigator
• Of legal adult age (according to local legislation) at screening
• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
• Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly.

Exclusion Criteria

• Previous systemic anti-cancer therapy within the specified timeframe from the last dose intake to the first dose of trial treatment as shown below:
• Any non-investigational drug, including anti-angiogenic antibodies (bevacizumab or ramucirumab) and anti-EGFR antibodies (cetuximab or panitumumab), within 14 days.
• Any investigational drug or other antibodies including immune checkpoint inhibitors, within 28 days.
• Radiation therapy within 4 weeks prior to start of treatment. However, palliative radiotherapy for symptomatic metastas