Clinical Trials /

A Study to Test Different Doses of BI 1701963 Alone and Combined With Trametinib in Patients With Different Types of Advanced Cancer (Solid Tumours With KRAS Mutation)

NCT04111458

Description:

The primary objective of this trial is to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of BI 1701963 as monotherapy and in combination with trametinib in patients with KRAS mutated solid tumours. Secondary objectives are to evaluate the safety and tolerability of BI 1701963 as monotherapy and in combination with trametinib, to characterise pharmacokinetics and pharmacodynamics, and to evaluate first efficacy signals.

Related Conditions:
  • Lung Adenocarcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Test Different Doses of BI 1701963 Alone and Combined With Trametinib in Patients With Different Types of Advanced Cancer (Solid Tumours With KRAS Mutation)
  • Official Title: A Phase I Open-label Dose Escalation Trial of BI 1701963 as Monotherapy and in Combination With Trametinib in Patients With KRAS Mutated Advanced or Metastatic Solid Tumours

Clinical Trial IDs

  • ORG STUDY ID: 1432-0001
  • SECONDARY ID: 2018-004757-24
  • NCT ID: NCT04111458

Conditions

  • Solid Tumors, KRAS Mutation

Interventions

DrugSynonymsArms
BI 1701963BI 1701963 monotherapy
TrametinibBI 1701963 + Trametinib

Purpose

The primary objective of this trial is to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of BI 1701963 as monotherapy and in combination with trametinib in patients with KRAS mutated solid tumours. Secondary objectives are to evaluate the safety and tolerability of BI 1701963 as monotherapy and in combination with trametinib, to characterise pharmacokinetics and pharmacodynamics, and to evaluate first efficacy signals.

Trial Arms

NameTypeDescriptionInterventions
BI 1701963 monotherapyExperimental
  • BI 1701963
BI 1701963 + TrametinibExperimental
  • BI 1701963
  • Trametinib

Eligibility Criteria

        Inclusion criteria:

        All parts

          -  Previously-identified activating Kirsten rat sarcoma viral oncogene homologue (KRAS)
             mutation in tumour tissue

          -  At least one target lesion that can be measured per Response Evaluation Criteria In
             Solid Tumours (RECIST) version 1.1.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Adequate organ function

          -  Age ≥18 years of age, or over the legal age of consent as required by local
             legislation.

          -  Signed and dated written informed consent in accordance with GCP and local legislation
             prior to admission to the trial.

          -  Women of childbearing potential who are not surgically sterilized must have a negative
             serum pregnancy test completed during the Screening period

          -  Further inclusion criteria apply

        Monotherapy and combination therapy dose escalation and monotherapy dose confirmation part

        - Documented disease progression despite appropriate prior standard therapies or for whom
        no standard therapy exists for their tumour type and disease stage

        Combination dose confirmation and expansion cohort

          -  Pathologically confirmed diagnosis of adenocarcinoma of the lung. Patients with mixed
             histology are eligible if adenocarcinoma is the predominant histology.

          -  Locally advanced stage IIIb or metastatic stage IV Non-small cell lung cancer (NSCLC)

          -  Patients must have received both chemotherapy and immunotherapy

        Exclusion criteria:

        All parts

          -  Previous anticancer chemotherapy within 3 weeks of the first administration of trial
             drug.

          -  Previous treatment with RAS, Mitogen-activated protein kinase (MAPK) or Son of
             sevenless 1 (SOS1) targeting agents

          -  Major surgery performed within 4 weeks prior to start of treatment

          -  Uncontrolled hypertension, congestive heart failure NYHA classification of ≥3,
             unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months
             prior to start of treatment

          -  Left ventricular ejection fraction (LVEF) <50 %

          -  Congenital long QT prolongation syndrome

          -  Mean resting corrected QT interval (QTcF) >470 msec

          -  Leptomeningeal carcinomatosis

          -  Presence or history of uncontrolled or symptomatic brain metastases

          -  Known pre-existing interstitial lung disease

          -  Known active hepatitis B infection (defined as presence of Hep B sAg and/or Hep B
             Deoxyribonucleic acid (DNA)), active hepatitis C infection (defined as presence of Hep
             C Ribonucleic acid (RNA))

          -  Active infectious disease

          -  Any history or presence of uncontrolled gastrointestinal disorders that could affect
             the intake and/or absorption of the trial drug

          -  History of retinal vein occlusion (RVO) or retinal pigment epithelial detachment
             (RPED)

          -  Further exclusion criteria apply

        Combination part

        - Hypersensitivity to any of the excipients listed in the current Summary of Product
        Characteristics (SmPC)/Package insert (PI) of trametinib
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose escalation (Part A) - Maximum tolerated dose (MTD) based on number of dose-limiting toxicities (DLTs)
Time Frame:4 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of BI 1701963: Cmax (maximum measured concentration of the analyte in plasma)
Time Frame:Up to 5 weeks
Safety Issue:
Description:
Measure:Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of BI 1701963: AUCτ (area under the concentration-time curve over a uniform dosing interval τ)
Time Frame:Up to 5 weeks
Safety Issue:
Description:
Measure:Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of trametinib: Cmax (maximum measured concentration of the analyte in plasma)
Time Frame:Up to 5 weeks
Safety Issue:
Description:
Measure:Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of trametinib: AUCτ (area under the concentration-time curve over a uniform dosing interval τ)
Time Frame:Up to 5 weeks
Safety Issue:
Description:
Measure:Dose confirmation (Part B) - Pharmacokinetic parameters of BI 1701963: Cmax (maximum measured concentration of the analyte in plasma)
Time Frame:Up to 5 weeks
Safety Issue:
Description:
Measure:Dose confirmation (Part B) - Pharmacokinetic parameters of BI 1701963: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)
Time Frame:Up to 5 weeks
Safety Issue:
Description:
Measure:Dose confirmation (Part B) - Pharmacokinetic parameters of midazolam: Cmax (maximum measured concentration of the analyte in plasma)
Time Frame:Up to 5 weeks
Safety Issue:
Description:
Measure:Dose confirmation (Part B) - Pharmacokinetic parameters of midazolam: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)
Time Frame:Up to 5 weeks
Safety Issue:
Description:
Measure:Dose confirmation (Part B) - Number of patients with Grade ≥3 treatment-related adverse events observed during the on-treatment period
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Dose confirmation (Part B) and expansion (Part C) - Duration of Objective response (OR)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Dose confirmation (Part B) and expansion (Part C) - Tumour shrinkage (in millimetres)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Dose confirmation (Part B) and expansion (Part C) - Progression-free survival
Time Frame:6 months
Safety Issue:
Description:
Measure:Dose confirmation (Part B) and expansion (Part C) - Number of patients with Grade ≥3 treatment-related adverse events observed during the on-treatment period
Time Frame:Up to 3 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Boehringer Ingelheim

Last Updated

December 10, 2019