A Study to Test Different Doses of BI 3011441 in Japanese People With Different Types of Advanced Cancer (NRAS/KRAS Mutation Positive)

Study Overview
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Brief Summary
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This study is open to Japanese adults with different types of advanced cancer that are positive for NRAS/KRAS mutations. This is a study in people for whom previous treatment was not successful or no standard treatment exists. The purpose of this study is to find the highest dose of BI 3011441 that Japanese people with advanced cancer can tolerate. BI 3011441 is a medicine that may turn off a signal by NRAS/KRAS that makes tumours grow. Participants take BI 3011441 as capsules once a day. Participants can stay in the study as long as they benefit from treatment and can tolerate it. The doctors collect information on any health problems of the participants.

Official Title
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A Phase I Open-label Trial of BI 3011441 in Japanese Patients With NRAS/KRAS Mutation Positive Advanced, Unresectable or Metastatic Refractory Solid Tumours

Conditions
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Solid Tumors, KRAS Mutation

Intervention / Treatment
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* Drug: BI 3011441


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be at least 20 years of age at screening. Signed and dated written informed consent in accordance with Good Clinical Practice(GCP) and local legislation prior to admission to the trial. Pathologically documented, locally-advanced or metastatic malignancy with previously identified activating Neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) or Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation based on local test. Provision of archival tumor tissue, if available, to confirm retrospectively NRAS or KRAS mutation status and for biomarker assessment. Willingness to undergo pre- and on-treatment tumour biopsies for pharmacodynamics and biomarker assessment. Patients can be enrolled without tumour biopsy upon agreement between the Investigator and the Sponsor if tumour biopsy is not feasible (Apply only to study site which agreed to conduct biopsy). Must have either progressed despite appropriate prior standard therapies or for whom no standard therapy exists for their tumour type and disease stage Must have at least one target lesion that can be measured per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 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 drugs. Radiotherapy within 4 weeks prior to first administration of BI 3011441 except as follows Palliative radiotherapy to regions other than the chest is allowed up to 2 weeks prior to start of treatment Single dose palliative radiotherapy for symptomatic metastasis within 2 weeks prior to start of treatment may be allowed but must be discussed with the sponsor. Major surgery within 4 weeks prior to start of treatment or scheduled during the projected course of the trial Previous treatment with a Rat sarcoma (RAS), Mitogen-activated protein kinase (MAPK) targeting agent Previous treatment with any investigational agent(s) or targeted treatment within 4 weeks (28 days) prior to start of trial drug or concurrent participation in another clinical trial with an investigational device or drug. Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the study medications Patients who have a history or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment or central serous retinopathy; for example, predisposing factors of RVO or central serous retinopathy include uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes. Patients who have visible retinal pathology that is considered a risk factor for RVO or central serous retinopathy as assessed by ophthalmic examination, such as: Evidence of new optic disc cupping Evidence of new visual field defects Intraocular pressure >21 mm Hg History or presence of cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of ≥2, unstable angina or poorly controlled arrhythmia which are considered as clinically relevant by the investigator; Myocardial infarction within 6 months prior to start of treatment. Uncontrolled hypertension is 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. Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 3011441<br> | Drug: BI 3011441<br>* BI 3011441 in different doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) defined as the highest dose with less than 25 percent (%) risk of the true Dose limiting toxicity (DLT) rate being equal or above 33 percent (%) during the MTD evaluation period. | The MTD evaluation period is defined as first treatment cycle (28 days). | up to 28 days | 
| Number of patients with Dose limiting toxicities (DLTs) in the Maximum tolerated dose (MTD) evaluation period. | The MTD evaluation period is defined as first treatment cycle (28 days). | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with Dose limiting toxicities (DLTs) during the entire on-treatment period. |  | up to two years | 
| Number of patients with Grade ≥3 treatment-related adverse events |  | up to two years | 
| Number of patients with treatment related adverse events at each dose level |  | up to two years | 
| Maximum measured concentration on Day 1 (Cmax) |  | Days 1 to 2 | 
| Maximum measured concentration at steady-state (Cmax,ss) |  | Days 15 to 16 | 
| Area under the concentration-time curve of BI 3011441 in plasma over the time interval from 0 to 24 h (AUC0-24) |  | Days 1 to 2 | 
| Area under the concentration-time curve of BI 3011441 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) |  | Days 15 to 16 |