A Study to Test Different Doses of BI 1823911 Alone and Combined With Other Medicines in People With Different Types of Advanced Cancer With KRAS Mutation

Launched by BOEHRINGER INGELHEIM · Jul 14, 2021

Keywords

ClinConnect Summary

This clinical trial is studying a new medicine called BI 1823911, which is being tested alone and in combination with another medicine, BI 1701963, for adults with advanced cancers that have a specific change in their genes known as a KRAS mutation. This mutation can cause tumors to grow more quickly, and the aim of the study is to find the highest dose of BI 1823911 that people can safely take. Researchers want to see if this treatment can help shrink tumors in patients who have not responded to previous therapies or for whom there are no other treatment options available.

To participate in this study, individuals must have certain types of advanced solid tumors, like lung or colorectal cancer, and their tumors must have the KRAS mutation. Participants will take the study medications in pill form once a day and will be regularly monitored by doctors for any side effects and to check the size of their tumors. The trial is currently active, but it’s not recruiting new participants at this time. If you or a loved one are considering this option, it's important to discuss it with your healthcare provider to see if you meet the eligibility criteria and to understand what to expect from the study.

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ALL

Eligibility criteria

• Inclusion Criteria:
• • Pathologically confirmed diagnosis of locally advanced or metastatic solid tumours, e.g. adenocarcinoma of the lung, colorectal cancer, pancreatic cancer or cholangiocarcinoma. Non-small cell lung cancer (NSCLC) patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
• • Documented disease progression despite appropriate prior standard therapies or for whom no standard therapy exists for their tumour type and disease stage.
• • KRAS mutation status: Kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation in tumour tissue or blood based on previously performed local testing using a validated test.
• • Provision of archival tumour tissue, if available, to confirm retrospectively KRAS G12C mutation status and for biomarker assessment.
• • At least one target lesion that can be measured per Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (radiated lesions do not qualify as target lesions). In patients who only have one target lesion, and a biopsy of the lesion is required, the baseline imaging must be performed before the biopsy or at the earliest two weeks after the biopsy.
• • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• * Adequate organ function as follows:
• • Absolute neutrophil count (ANC) ≥1.5 x 10\^9/L (equivalent values: ≥ 1.5 x 10³/μL or ≥ 1500/mm³); hemoglobin ≥9.0 g/dL (equivalent values: ≥ 90 g/L or ≥ 5.6 mmol/L); platelets ≥100 x 10\^9/L (equivalent values: ≥ 100 x 10³/μL or ≥ 100 x 10³/mm³) without the use of haematopoietic growth factors.
• • Total bilirubin ≤1.5 times the upper limit of normal (ULN), or ≤4 x ULN for patients who are known to have Gilbert's syndrome.
• • Creatinine ≤1.5 x ULN. If creatinine is \>1.5 x ULN, patient is eligible if concurrent creatinine clearance ≥50 mL/min (equivalent value: 0.84mL/s) (measured or calculated by Cockcroft-Gault formula).
• • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 x ULN, for patients with liver metastases ≤5 x ULN.
• • Age ≥18 years of age, or over the legal age of consent as required by local legislation.
• • Further inclusion criteria apply.
• Exclusion Criteria:
• • Previous anticancer chemotherapy within 3 weeks of the first administration of trial drug. Previous anticancer hormonal treatment or anticancer immunotherapy within 2 weeks of the first administration of trial drug.
• • Previous treatment with Rat Sarcoma (RAS), Mitogen-activated protein kinase (MAPK) or Son of sevenless 1 (SOS1) targeting agents (only for monotherapy Parts A, B, and C).
• • Radiotherapy within 2 weeks prior to start of treatment, provided recovery from related toxicity.
• • Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to start of treatment or planned during the projected course of the trial, e.g. hip replacement.
• • Previous treatment with any investigational agent(s) or targeted treatment within 28 days prior to start of treatment or 5 half-lives, whichever is shorter.
• • Known history of hypersensitivity to any of the excipients of BI 1823911 tablets, or any contraindication to Midazolam (for Monotherapy Part B only).
• • History or presence of cardiovascular abnormalities such as congestive heart failure New York Heart Association (NYHA) classification of ≥3, unstable angina or poorly controlled arrhythmia which are considered clinically relevant by the Investigator. Myocardial infarction within 6 months prior to start of treatment. Uncontrolled hypertension defined as: Blood pressure (BP) measured in a rested and relaxed condition, where systolic BP \>=140 mmHg, or diastolic BP \>= 90 mmHg, with or without medication.
• • Left ventricular ejection fraction (LVEF) \<50%. Further exclusion criteria apply.