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This Study Aims to Find the Best Doses of BI 836880 Combined With BI 754091 in Patients With a Certain Type of Advanced Lung Cancer (NSCLC)

NCT03468426

Description:

PART 1: Primary objective: - To determine the Recommended Phase 2 Dose (RP2D) of BI 836880 in combination with BI 754091 in patients with locally advanced or metastatic non-squamous NSCLC who progressed during or after first line (in case of checkpoint inhibitor naïve patients) platinum-based therapy and patients who relapsed after completion of at least 2 cycles (in case of checkpoint inhibitor relapsing patients) of platinum-based chemotherapy and a checkpoint inhibitor treatment (monotherapy or in combination with chemotherapy). Secondary objective: - To provide safety data - To evaluate the basic pharmacokinetics of BI 836880 and BI 754091 during combination therapy after the first and fourth infusion cycle. PART 2: Primary objective: - To assess anti-tumour activity of BI 836880 in combination with BI 754091 in check point inhibitor naïve patients with locally advanced or metastatic non-squamous NSCLC who progressed during or after first line platinum-based treatment . - Cohort A: Patients with locally advanced or metastatic non-squamous NSCLC with low PD-L1 expression (PD-L1 expression in 1-49% of tumor cells) - Cohort B: Patients with locally advanced or metastatic non-squamous NSCLC with high PD-L1 expression (PD-L1 expression in ≥ 50% of tumor cells) Secondary objective: - To provide preliminary safety data and the secondary measures of clinical efficacy including disease control (DC), duration of objective response (DoR), progression free survival (PFS), and tumour shrinkage - To evaluate the basic pharmacokinetics of BI 836880 and BI 754091 during combination therapy after the first and fourth infusion cycle.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: This Study Aims to Find the Best Doses of BI 836880 Combined With BI 754091 in Patients With a Certain Type of Advanced Lung Cancer (NSCLC)
  • Official Title: An Open Label Phase Ib Dose Finding Study of BI 836880 in Combination With BI 754091 to Characterize Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy in Check Point Inhibitor naïve Patient With Locally Advanced or Metastatic Non-squamous Non-Small Cell Lung Cancer Who Progressed During or After First Line Platinum-based Treatment

Clinical Trial IDs

  • ORG STUDY ID: 1336-0011
  • SECONDARY ID: 2017-001378-41
  • NCT ID: NCT03468426

Conditions

  • Non-squamous, Non-Small-Cell Lung Cancer

Interventions

DrugSynonymsArms
BI 836880BI 836880 + BI 754091
BI 754091BI 836880 + BI 754091

Purpose

PART 1: Primary objective: - To determine the Recommended Phase 2 Dose (RP2D) of BI 836880 in combination with BI 754091 in check point inhibitor naïve patients with locally advanced or metastatic non-squamous NSCLC who progressed during or after first line platinum based treatment. Secondary objective: - To provide safety data - To evaluate the basic pharmacokinetics of BI 836880 and BI 754091 during combination therapy after the first and fourth infusion cycle. PART 2: Primary objective: - To assess anti-tumour activity of BI 836880 in combination with BI 754091 in check point inhibitor naïve patients with locally advanced or metastatic non-squamous NSCLC who progressed during or after first line platinum-based treatment . - Cohort A: Patients with locally advanced or metastatic non-squamous NSCLC with low PD-L1 expression (PD-L1 expression in 1-49% of tumor cells) - Cohort B: Patients with locally advanced or metastatic non-squamous NSCLC with high PD-L1 expression (PD-L1 expression in ≥ 50% of tumor cells) Secondary objective: - To provide preliminary safety data and the secondary measures of clinical efficacy including disease control (DC), duration of objective response (DoR), progression free survival (PFS), and tumour shrinkage - To evaluate the basic pharmacokinetics of BI 836880 and BI 754091 during combination therapy after the first and fourth infusion cycle.

Trial Arms

NameTypeDescriptionInterventions
BI 836880 + BI 754091Experimental
  • BI 836880
  • BI 754091

Eligibility Criteria

        Inclusion Criteria:

          -  Of full age (according to local legislation, usually >= 18 years) at screening.

          -  Pathologically confirmed locally advanced or metastatic non-squamous Non-Small Cell
             Lung Cancer (NSCLC) with Programmed death-ligand 1 (PDL-1) expression available and
             >1% by IHC

          -  No previous treatment with check-point inhibitor.

          -  Documented disease progression or relapse (based on investigator's assessment) during
             or after completion of at least 2 cycles of platinum-based chemotherapy as first line
             treatment of Stage IIIB/IV NSCLC. This includes patients relapsing within 6 months of
             completing (neo)adjuvant/curative-intent chemotherapy or chemoradiotherapy

          -  At least one target lesion (outside the brain) that can be accurately measured per
             Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.

          -  Lesion with a diameter = 2cm assessed by radiologist as suitable for Dynamic
             Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) evaluation (Mandatory in Part
             1, optional in Part 2)

          -  Eastern Cooperative Oncology Group (ECOG) performance status <= 1

          -  Life expectancy >= 3 months after start of the treatment in the opinion of the
             investigator

          -  Recovery from all reversible adverse events of previous anti-cancer therapies to
             baseline or Common Terminology Criteria for Adverse Events (CTCAE) grade 1, except for
             alopecia (any grade), sensory peripheral neuropathy , must be <= CTCAE grade 2 or
             considered not clinically significant.

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

          -  Adequate organ function defined as all of the following (all screening labs should be
             performed at local lab within 10 days prior to treatment initiation)

          -  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
             per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used
             consistently and correctly, starting with the screening visit and through 150 days
             after the last dose of BI 836880 and BI 754091 treatment, respectively. A list of
             contraception methods meeting these criteria is provided in the patient information.

        Exclusion criteria:

          -  Known hypersensitivity to the trial drugs or their excipients or risk of allergic of
             anaphylactic reaction to drug product according to Investigator judgement (e.g.
             patient with history of anaphylactic reaction or autoimmune disease that is not
             controlled by nonsteroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids,
             or the equivalent of </= 10 mg/day prednisone).

          -  Known immunodeficiency virus infection or an active hepatitis B or C virus infection.

          -  History of severe hypersensitivity reactions to other mAbs.

          -  Immunosuppressive corticosteroid doses (> 10 mg prednisone daily or equivalent) within
             4 weeks prior to the first dose of trial medication.

          -  Current or prior treatment with any systemic anti-cancer therapy either within 28 days
             or a minimum of 5 half-lives, whichever is shorter before start of treatment.

          -  Serious concomitant disease, especially those affecting compliance with trial
             requirements or which are considered relevant for the evaluation of the endpoints of
             the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers
             (gastrointestinal 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.

          -  Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment,
             or planned surgical procedures during the trial period.

          -  Patients with personal or family history of QT prolongation and/or long QT syndrome,
             or prolonged QTcF at baseline (> 470 ms). QTcF will be calculated by Investigator as
             the mean of the 3 electrocardiograms (ECGs) taken at screening.

          -  Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension,
             unstable angina, history of infarction within past 6 months, congestive heart failure
             > NYHA II). Uncontrolled hypertension defined as: Blood pressure in rested and relaxed
             condition >= 140 mmHg, systolic or >= 90 mmHg diastolic (with or without medication)

          -  Left Ventricular Ejection Fraction (LVEF) < 50%

          -  History of severe haemorrhagic or thromboembolic event in the past 12 months
             (excluding central venous catheter thrombosis and peripheral deep vein thrombosis).

          -  Known inherited predisposition to bleeding or to thrombosis in the opinion of the
             investigator.

          -  Patient with brain metastases that are symptomatic and/or require therapy.

          -  Patients who require full-dose anticoagulation (according to local guidelines). No
             Vitamin K antagonist and other anticoagulation allowed; Low-Molecular-Weight Heparin
             (LMWH) allowed only for prevention not for curative treatment.

          -  History of pneumonitis within the last 5 years

          -  Patients who are under judicial protection and patients who are legally
             institutionalized.

          -  Patients unable or unwilling to comply with protocol

          -  Previous enrolment in this trial (Part 1 or Part 2).

          -  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 in the trial
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:PART 1: Number of patients with Dose Limiting Toxicities (DLTs) within the first cycle of treatment
Time Frame:Up to 3 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:PART 1:Adverse events (AEs), drug related AEs, drug related AEs leading to dose reduction or discontinuation during treatment period
Time Frame:Up to 3 weeks
Safety Issue:
Description:
Measure:PART 1: AUC 0-504h (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours after the first and fourth infusion cycle)
Time Frame:Up to 504 hours after first and fourth infusion cycle
Safety Issue:
Description:
Measure:PART 2:Adverse events (AEs), drug related AEs, drug related AEs leading to dose reduction or discontinuation during treatment period
Time Frame:Up to 3 weeks
Safety Issue:
Description:
Measure:PART 2: Disease control (DC)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:PART 2: Duration of objective response (DoR)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:PART 2: Progression-free survival (PFS)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:PART 2: Tumour shrinkage (in millimeters)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:PART 2: AUC 0-504h (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours after the first and fourth infusion cycle)
Time Frame:Up to 504 hours after first and fourth infusion cycle
Safety Issue:
Description:
Measure:PART 1: Cmax (maximum measured concentration of the analyte in plasma)
Time Frame:Up to 12 weeks
Safety Issue:
Description:
Measure:PART 1: tmax (time from dosing to maximum measured concentration of the analyte in plasma)
Time Frame:Up to 12 weeks
Safety Issue:
Description:
Measure:PART 2: Cmax (maximum measured concentration of the analyte in plasma)
Time Frame:Up to 12 weeks
Safety Issue:
Description:
Measure:PART 2: tmax (time from dosing to maximum measured concentration of the analyte in plasma)
Time Frame:Up to 12 weeks
Safety Issue:
Description:

Details

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

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