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

NCT04973163 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 1472-00012021-000460-29
• Study Type: interventional
• Target: 30
• Locations: 4 countries
• Sites: 9

Brief Summary

This study is open to adults with different types of advanced or metastatic cancer (including lung cancer, colorectal cancer, pancreatic cancer, and bile duct cancer). This study is for people for whom previous treatment was not successful or no treatment exists. People who have a tumour with a KRAS mutation can participate in the study. A KRAS mutation makes tumours grow faster. BI 1823911 and BI 1701963 are medicines that may turn off KRAS, each in a different way. In this study, BI 1823911 is given to people for the first time. The purpose of this study is to find the highest dose of BI 1823911 that people can tolerate when taken alone and together with BI 1701963. The most suitable dose is used to find out whether BI 1823911 alone and in combination with BI 1701963 can make tumours shrink. Participants can stay in the study as long as they benefit from treatment and can tolerate it. During this time, participants take tablets of BI 1823911 alone or in combination with BI 1701963 once a day. The doctors regularly monitor the size of the tumour. Doctors also regularly record any unwanted effects and check participant's health.

Conditions

Solid Tumors, KRAS Mutation

Outcome Measures

Primary Outcomes (2)

• Dose escalation (Part A) - Monotherapy and combination therapy: Number of patients experiencing Dose limiting toxicities (DLTs) during the Maximum tolerated dose (MTD) evaluation period for BI 1823911 in monotherapy and in each combination

  DLTs are graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  up to 28 days

• Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Objective response (OR) defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR)

  BOR is determined according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. BOR will consider all tumour assessments from first treatment administration until the earliest of disease progression, death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent.

  up to 39 months

Secondary Outcomes (14)

• Dose escalation (Part A) - Monotherapy and combination therapy: Number of patients experiencing DLTs during all treatment cycles for BI 1823911 in monotherapy and in each combination

  up to 39 months

• Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Objective response (OR)

  up to 39 months

• Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Duration of OR

  up to 39 months

• Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Tumour shrinkage (in millimetres)

  up to 39 months

• Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Progression-free survival (PFS) rate

  at month 6

Study Arms (2)

Monotherapy Arm

EXPERIMENTAL

Each arm consists of three parts (dose escalation (A), dose confirmation (B), and dose expansion (C).

Drug: BI 1823911; Drug: Midazolam

Combination Therapy Arm

EXPERIMENTAL

Will be started after confirmation of safety in the Monotherapy Arm. Each arm consists of three parts (dose escalation (A), dose confirmation (B), and dose expansion (C).

Drug: BI 1823911; Drug: BI 1701963

Interventions

BI 1823911 DRUG

BI 1823911

Combination Therapy Arm; Monotherapy Arm

BI 1701963 DRUG

BI 1701963

Combination Therapy Arm

Midazolam DRUG

Midazolam - only administered in Part B (dose confirmation) of the Monotherapy Arm

Monotherapy Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (9)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Sarah Cannon Research Institute at Mary Crowley

Dallas, Texas, 75230, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Brussels - HOSP Jules Bordet

Anderlecht/Brussels-Capital, 1070, Belgium

Location

Edegem - UNIV UZ Antwerpen

Edegem/Antwerpen, 2650, Belgium

Location

Universitair Ziekenhuis Gent

Gent/Oost-Vlaanderen, 9000, Belgium

Location

UZ Leuven

Leuven/Vlaams-Brabant, 3000, Belgium

Location

Hospital Universitari Vall D Hebron

Barcelona, 08035, Spain

Location

The Christie

Manchester, M20 4BX, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Interventions

Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The following parts will be included in this trial: * First: Monotherapy Arm * After confirmation of safety: Combination Therapy Arm Each arm consists of three parts (dose escalation (A), dose confirmation (B), and dose expansion (C)).

Study Record Dates

• First Submitted: July 14, 2021
• First Posted: July 22, 2021
• Study Start: September 9, 2021
• Primary Completion (Estimated): November 29, 2026
• Study Completion (Estimated): December 27, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); US (3); GB (1); BE (4)