Clinical Trials /

A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread

NCT03166631

Description:

The main objective of the dose-escalation parts of the trial is to determine the maximum tolerated dose (MTD), based on the frequency of patients experiencing dose-limiting toxicities (DLTs), and/or the recommended dose for further development of BI 891065 monotherapy as well as of BI 891065 in combination with BI 754091, and to evaluate its safety and tolerability by monitoring the occurrence and severity of adverse events (AEs). Secondary objectives are the determination of the pharmacokinetic (PK) profile of BI 891065 monotherapy as well as of BI 891065 in combination with BI 754091, and the preliminary assessment of anti-tumour activity.

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread
  • Official Title: An Open-label Phase I Dose Finding Trial With BI 891065 Alone and in Combination With BI 754091 to Characterise Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy in Patients With Advanced and/or Metastatic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 1379-0001
  • SECONDARY ID: 2017-000465-74
  • NCT ID: NCT03166631

Conditions

  • Neoplasms
  • Neoplasm Metastasis
  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
BI 891065Part A
BI 754091Part B

Purpose

The main objective of the dose-escalation parts of the trial is to determine the maximum tolerated dose (MTD), based on the frequency of patients experiencing dose-limiting toxicities (DLTs), and/or the recommended dose for further development of BI 891065 monotherapy as well as of BI 891065 in combination with BI 754091, and to evaluate its safety and tolerability by monitoring the occurrence and severity of adverse events (AEs). Secondary objectives are the determination of the pharmacokinetic (PK) profile of BI 891065 monotherapy as well as of BI 891065 in combination with BI 754091, and the preliminary assessment of anti-tumour activity.

Trial Arms

NameTypeDescriptionInterventions
Part AExperimentalBI 891065 alone (Solid Tumours)
  • BI 891065
Part BExperimentalBI 891065 in combination with BI 754091 (Solid Tumours)
  • BI 891065
  • BI 754091
Part CExperimentalBI 891065 in combination with BI 754091 (Non Small Cell Lung Cancer)
  • BI 891065
  • BI 754091

Eligibility Criteria

        Inclusion criteria:

          -  Provision of signed and dated, written ICF in accordance with ICH-GCP and local
             legislation prior to any trial-specific procedures, sampling, or analyses

          -  Patients ≥18 years-of-age at the time of signature of the ICF

          -  Male or female patients. Women of childbearing potential (WOCBP) and men able to
             father a child must be ready and able to use highly effective methods of birth control
             (that result in a low failure rate of less than 1% per year when used consistently and
             correctly)during trial participation and for at least 6 months after the last
             administration of trial medication. A list of contraception methods meeting these
             criteria is provided in the patient information.

          -  Eastern Cooperative Oncology Group (ECOG) score: 0 to 1

          -  Life expectancy of at least 12 weeks after the start of the treatment according to the
             Investigator's judgement

          -  For Parts A and B: Patients with a confirmed diagnosis of advanced, unresectable
             and/or metastatic solid tumours, who have failed standard treatment, or for whom no
             therapy of proven efficacy exists, or who are not amenable to standard therapies.
             Measurable lesions according to RECIST Version 1.1 must be present.

          -  For Parts B and C (Cohort 1): Patients must have measurable disease per RECIST
             v1.1,must have at least 1 tumour lesion amenable to biopsy, and must be willing to
             undergo a biopsy prior to first treatment and after 6 weeks on therapy.

          -  For Part C: Patients with a confirmed diagnosis of advanced NSCLC who have been
             treated with combination of platinum-based chemotherapy as first-line therapy.

          -  For Part C: Patients within 6 to 16 weeks are not responding to treatment with an anti
             PD-1/anti PD-L1 mAb second line therapy, and who are no longer benefitting from the
             previous therapy in the opinion of the Investigator.

        Exclusion criteria:

          -  Major surgery (major according to the Investigator's assessment) performed within 12
             weeks prior to randomization or planned within 12 months after screening (e.g., hip
             replacement)

          -  Presence of other active invasive cancers other than the one treated in this trial
             within 5 years prior to screening, except appropriately treated basal cell carcinoma
             of the skin, or in situ carcinoma of uterine cervix, or other local tumours considered
             cured by local treatment

          -  Patients who must or wish to continue the intake of restricted medications or any drug
             considered likely to interfere with the safe conduct of the trial

          -  Previous administration of BI 891065 or BI 754091

          -  Currently enrolled in another investigational device or drug trial, or less than 30
             days since ending another investigational device or drug trial(s), or receiving other
             investigational treatments.

          -  Patients who have been treated with any other anticancer drug within 4 weeks or within
             5 half-life periods (whichever come earlier) prior to first administration of BI
             891065

          -  Persistent toxicity from previous treatments that has not resolved to ≤ Grade 1
             (except for alopecia)

          -  Active, known or suspected autoimmune disease except vitiligo or resolved asthma/atopy

          -  Interstitial lung disease

          -  Any of the following cardiac criteria:

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

               -  Any clinically important abnormalities (as assessed by the investigator) in
                  rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle
                  branch block, third degree heart block

               -  Any factors that increase the risk of QTc prolongation or risk of arrhythmic
                  events such as heart failure, hypokalaemia, congenital long QT syndrome, family
                  history of long QT syndrome or unexplained sudden death under 40 years-of-age, or
                  any concomitant medication known to prolong the QT interval

               -  Patients with an ejection fraction (EF) <55% or the lower limit of normal of the
                  institutional standard will be excluded. Only in cases where the Investigator (or
                  the treating physician or both) suspects cardiac disease with negative effect on
                  the EF, will the EF be measured during screening using an appropriate method
                  according to local standards to confirm eligibility (e.g., echocardiogram [ECHO],
                  multi-gated acquisition scan [MUGA]). A historic measurement of EF no older than
                  6 months prior to first administration of study drug can be accepted provided
                  that there is clinical evidence that the EF value has not worsened since this
                  measurement in the opinion of the Investigator or of the treating physician or
                  both.

          -  Out of range laboratory values are defined as:

               -  Alanine transaminase (ALT) and aspartate amino transferase (AST) >3 times the ULN
                  if no demonstrable liver metastases or >5 times ULN in the presence of liver
                  metastases

               -  Total bilirubin >1.5 times ULN, except for patients with Gilbert's syndrome who
                  are excluded if total bilirubin >3.0 times ULN or direct bilirubin >1.5 times ULN

          -  Human immunodeficiency virus (HIV) infection, acute or chronic viral hepatitis

          -  Known hypersensitivity to the trial drugs or their excipients

          -  Serious concomitant disease or medical condition affecting compliance with trial
             requirements or which are considered relevant for the evaluation of the efficacy or
             safety of the trial drug, such as cardiac, neurologic, psychiatric, infectious disease
             or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may
             increase the risk associated with trial participation or trial drug administration,
             and in the judgment of the Investigator would make the patient inappropriate for entry
             into the trial.

          -  Chronic alcohol or drug abuse or any condition that, in the Investigator's opinion,
             makes them an unreliable trial patient or unlikely to complete the trial

          -  Women who are pregnant, nursing, or who plan to become pregnant while in the trial and
             for at least 6 months after the last administration of trial medication.

          -  Men who plan to father a child while in the trial and for at least 6 months after the
             last administration of trial medication.

          -  Known presence of symptomatic central nervous system (CNS) metastases, unless
             asymptomatic and off corticosteroids and/or anti-convulsant therapy for at least 2
             weeks prior start of treatment

          -  Patients receiving systemic treatment with any immunosuppressive medication within 1
             week prior treatment start (steroids of max. 10 mg prednisolone equivalent per day are
             allowed, topical and inhaled steroids are not considered as immunosuppressive).

          -  For Parts A and B: Patients with known epidermal growth factor receptor (EGFR), known
             anaplastic lymphoma kinase (ALK), or known ROS Proto-Oncogene 1 (ROS1) genomic tumour
             aberrations, unless disease has progressed following available EGFR or ALK targeted
             therapy (including osimertinib for EGFR T790M-mutated NSCLC)

          -  Out of range lab values as defined:

               -  Absolute neutrophil count (ANC) <1.5 x 109/L (<1500/mm3)

               -  Platelet (PLT) count <100 x 109/L

          -  Haemoglobin <90 g/L (<9 g/dL)

             -- Creatinine >1.5 times ULN (patients may enter if creatinine is >1.5 x ULN and
             estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2) (Chronic Kidney
             Disease Epidemiology [CKD-EPI] Collaboration equation); confirmation of eGRF is only
             required when creatinine is >1.5 X ULN.

          -  For Part C: Patients with EGFR, ALK, or (if known) ROS1 genomic tumor aberrations

          -  For Part C: Patients with any CTLA-4 therapy

          -  For Part C: One or more lines of anti-cancer therapy between previous
             anti-PD-1/anti-PDL1 mAb therapy and study entry.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A - Maximum tolerated dose of BI 891065
Time Frame:9 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Part A - The number of patients with Dose-limiting toxicities (DLTs) observed during the entire treatment period.
Time Frame:12 months
Safety Issue:
Description:
Measure:Part A - Cmax(,ss) of BI 891065 in the first treatment cycle.
Time Frame:3 weeks
Safety Issue:
Description:
Measure:Part A - Objective response (OR) based on RECIST v1.1.
Time Frame:12 months
Safety Issue:
Description:
Measure:Part B - The number of patients with Dose-limiting toxicities (DLTs) observed during the entire treatment period.
Time Frame:12 months
Safety Issue:
Description:
Measure:Part B - Cmax(,ss) of BI 891065
Time Frame:3 weeks
Safety Issue:
Description:
Measure:Part B - Objective response (OR) based on RECIST v1.1.
Time Frame:12 months
Safety Issue:
Description:
Measure:Part C - Duration of Objective response (OR) based on RECIST 1.1 (for the NSCLC cohort)
Time Frame:18 months
Safety Issue:
Description:
Measure:Part A - AUC0-tz of BI 891065 in the first treatment cycle.
Time Frame:3 weeks
Safety Issue:
Description:
Measure:Part A - AUC tau,ss of BI 891065 in the first treatment cycle.
Time Frame:3 weeks
Safety Issue:
Description:
Measure:Part B - AUC0-tz of BI 891065
Time Frame:3 weeks
Safety Issue:
Description:
Measure:Part B - AUCtau,ss of BI 891065
Time Frame:3 weeks
Safety Issue:
Description:
Measure:Part B - Cmax of BI 754091 in the first treatment cycle.
Time Frame:3 weeks
Safety Issue:
Description:
Measure:Part B - AUC0-tz of BI 754091 in the first treatment cycle.
Time Frame:3 weeks
Safety Issue:
Description:

Details

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

Last Updated

October 2, 2017