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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04973163
Recruitment Status : Recruiting
First Posted : July 22, 2021
Last Update Posted : March 7, 2023
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Description
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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.


Condition or disease Intervention/treatment Phase
Solid Tumors, KRAS Mutation Drug: BI 1823911 Drug: BI 1701963 Drug: Midazolam Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

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)).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ia/Ib, Open-label, Multicentre Dose-escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Preliminary Efficacy of BI 1823911 as a Monotherapy and in Combination With Other Anti-cancer Therapies in Patients With Advanced or Metastatic Solid Tumours Expressing KRAS G12C Mutation
Actual Study Start Date : August 3, 2021
Estimated Primary Completion Date : July 26, 2024
Estimated Study Completion Date : July 26, 2024
Arms and Interventions
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Arm Intervention/treatment
Experimental: Monotherapy Arm
Each arm consists of three parts (dose escalation (A), dose confirmation (B), and dose expansion (C).
 Drug: BI 1823911
BI 1823911

Drug: Midazolam
Midazolam - only administered in Part B (dose confirmation) of the Monotherapy Arm
Experimental: Combination Therapy Arm
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
BI 1823911

Drug: BI 1701963
BI 1701963


Outcome Measures
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Primary Outcome Measures :
  1. 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 [ Time Frame: up to 28 days ]
    DLTs are graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  2. 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) [ Time Frame: up to 39 months ]

    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.



Secondary Outcome Measures :
  1. 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 [ Time Frame: up to 39 months ]
  2. Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Objective response (OR) [ Time Frame: up to 39 months ]

    OR is defined as best overall response (BOR) of complete response (CR) or partial response (PR), both regardless of confirmation.

    BOR is determined according to 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.


  3. Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Duration of OR [ Time Frame: up to 39 months ]
    Duration of OR is defined as the time from first documented CR or PR until disease progression or death (whichever occurs first) among patients with OR.

  4. Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Tumour shrinkage (in millimetres) [ Time Frame: up to 39 months ]
    Tumour shrinkage is defined as the difference between the minimum post-baseline sum of diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) and the baseline sum of longest diameters of the same set of target lesions.

  5. Dose confirmation (Part B) and expansion (Part C) - Monotherapy and combination therapy: Progression-free survival (PFS) rate [ Time Frame: at month 6 ]
    PFS is defined as the time from first treatment administration until tumour progression according to RECIST version 1.1 or death from any cause, whichever occurs earlier.

  6. All study parts: Number of patients with adverse events during the on-treatment period [ Time Frame: up to 39 months ]
  7. All study parts, BI 1823911: Maximum concentration (Cmax) [ Time Frame: up to 24 hours ]
  8. All study parts, BI 1823911: Steady state concentration (Css) [ Time Frame: up to 24 hours ]
  9. All study parts, BI 1823911: Area under the plasma concentration-time curve from time zero to time t (AUCτ) [ Time Frame: up to 24 hours ]
  10. All study parts, BI 1823911: Area under the plasma concentration-time curve at steady state (AUCss) [ Time Frame: up to 24 hours ]
  11. All study parts, BI 1701963: Maximum concentration (Cmax) [ Time Frame: up to 24 hours ]
  12. All study parts, BI 1701963: Steady state concentration (Css) [ Time Frame: up to 24 hours ]
  13. All study parts, BI 1701963: Area under the plasma concentration-time curve from time zero to time t (AUCτ) [ Time Frame: up to 24 hours ]
  14. All study parts, BI 1701963: Area under the plasma concentration-time curve at steady state (AUCss) [ Time Frame: up to 24 hours ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04973163


Contacts
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Contact: Boehringer Ingelheim 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com

Locations
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United States, Texas
Mary Crowley Cancer Research Center Recruiting
Dallas, Texas, United States, 75201
Contact: Boehringer Ingelheim    833-602-2368    unitedstates@bitrialsupport.com   
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Boehringer Ingelheim    833-602-2368    unitedstates@bitrialsupport.com   
Belgium
Brussels - HOSP Jules Bordet Recruiting
Anderlecht, Belgium, 1070
Contact: Boehringer Ingelheim    080049616    belgique@bitrialsupport.com   
Edegem - UNIV UZ Antwerpen Recruiting
Edegem, Belgium, 2650
Contact: Boehringer Ingelheim    080049616    belgique@bitrialsupport.com   
UNIV UZ Gent Recruiting
Gent, Belgium, 9000
Contact: Boehringer Ingelheim    080049616    belgique@bitrialsupport.com   
UZ Leuven Recruiting
Leuven, Belgium, 3000
Contact: Boehringer Ingelheim    080049616    belgique@bitrialsupport.com   
Spain
Hospital Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Boehringer Ingelheim    900876092    espana@bitrialsupport.com   
United Kingdom
The Christie Hospital Recruiting
Manchester, United Kingdom, M20 4BX
Contact: Boehringer Ingelheim    08000514022    unitedkingdom@bitrialsupport.com   
Sponsors and Collaborators
Boehringer Ingelheim
More Information
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Additional Information:

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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT04973163    
Other Study ID Numbers: 1472-0001
2021-000460-29 ( EudraCT Number )
First Posted: July 22, 2021    Key Record Dates
Last Update Posted: March 7, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

  1. studies in products where Boehringer Ingelheim is not the license holder;
  2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
  3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Midazolam
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
 Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action