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This Study Tests the New Medicine BI 754111 Alone or in Combination With Another New Substance BI 754091 in Patients With Advanced Cancer. The Study Tests Different Doses to Find the Best Dose for Continuous Treatment.

NCT03156114

Description:

This study tests the new medicine BI 754111 alone or in combination with BI 754091 in patients with advanced cancer. The study tests different doses to find the best dose for continuous treatment

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: This Study Tests the New Medicine BI 754111 Alone or in Combination With Another New Substance BI 754091 in Patients With Advanced Cancer. The Study Tests Different Doses to Find the Best Dose for Continuous Treatment.
  • Official Title: An Open Label, Phase I Dose-finding Study of BI 754111 in Combination With BI 754091 in Patients With Advanced Solid Cancers Followed by Expansion Cohorts at the Selected Dose of the Combination in Patients With Non-small Cell Lung Cancer and Other Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 1381-0002
  • SECONDARY ID: 2017-005042-29
  • NCT ID: NCT03156114

Conditions

  • Neoplasms
  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
BI 754111Part I - Dose--Escalation
BI 754091Part I - Dose--Escalation

Purpose

This study tests the new medicine BI 754111 alone or in combination with BI 754091 in patients with advanced cancer. The study tests different doses to find the best dose for continuous treatment

Trial Arms

NameTypeDescriptionInterventions
Part I - Dose--EscalationExperimental
  • BI 754111
  • BI 754091
Part II - Dose-ExpansionExperimental
  • BI 754111
  • BI 754091

Eligibility Criteria

        Inclusion Criteria:

          -  Provision of signed and dated, written Informed consent form [ICF] prior to any
             trial-specific procedures, sampling, or analyses

          -  Patients ≥18 years of age at the time of signature of the Informed consent form [ICF]

          -  Part I (dose escalation):

             --Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic
             solid tumours (any type)

               -  For whom no therapy of proven efficacy exists, or who are not amenable to
                  standard therapies.

               -  Must have measurable lesions according to Response Evaluation Criteria in Solid
                  Tumours (RECIST) v1.1

               -  Previous treatment with an anti-programmed cell death 1 (receptor) (PD-1)
                  monoclonal antibody (mAb) is allowed as long as the last administration of the
                  anti-PD-1 mAb on the previous treatment is a minimum of 60 days prior to starting
                  treatment in this trial.

          -  Part II (dose expansion):

               -  Patients must have measurable disease per RECIST v1.1 criteria, must have at
                  least 1 tumour lesion amenable to biopsy, and must be medically fit and willing
                  to undergo a biopsy before first treatment (if adequate archival tissue is not
                  available) and, unless clinically contraindicated, after 6 weeks on therapy.

               -  Dose Expansion Cohorts:

                    -  Second and 3rd line Non-small cell lung cancer (NSCLC) patients:

                         -  Must have progressed on anti-PD-1 or anti-programmed cell death ligand
                            1 (PD-L1) treatment after having achieved radiologically confirmed
                            benefit (minimum of stable disease)

                         -  Must have had a minimum duration of benefit of 8 months for
                            non-squamous NSCLC patients who received immunotherapy plus
                            chemotherapy in a first line setting, or 6 months for all other
                            patients, and minimum treatment duration of 2 months on the previous
                            anti-PD-1 or anti-PD-L1 treatment without experiencing disease
                            progression during that period.

                         -  The anti-PD-1- or anti-PD-L1-containing treatment must have been the
                            latest treatment regimen prior to enrolling in this trial

                         -  Must be within >4 and <12 weeks since the latest treatment and their
                            first dose in this trial. Patients who have had anti-PD-1 or anti-PD-L1
                            monotherapy as their first-line NSCLC treatment regimen must have a
                            PD-L1 expression level of ≥1% at baseline (local validated testing).

                    -  Anti-PD-1 or anti-PD-L1 treatment-naïve patients with microsatellite stable
                       mCRC:

                         -  Patients must have had ≥ 1 line treatment

                         -  Must have microsatellite stable disease (identified using any validated
                            test)

                         -  Must be anti-PD-1 and anti-PD-L1 treatment naïve

                    -  Anti-PD-1 or anti-PD-L1 pretreated patients with any high Tumour mutational
                       burden (TMB) (≥10 mutations/Mb) and/or Microsatellite instability high
                       (MSI-H) and/or DNA MMRd solid tumours

                         -  Patients must have high TMB (≥ 10 mutations/Mb) and/or MSI-H and/or DNA
                            mismatch repair deficient (MMRd) (measured using any validated test).

                         -  Patients must have received 1 prior anti-PD-1 or anti-PD-L1 treatment
                            regimen.

                    -  1st-line squamous or non-squamous NSCLC patients:

                         -  Patients must be treatment naïve

                         -  Must be EGFR wild type

                         -  Any PD-L1 expression level. However, the number of patients with high
                            level of PD-L1 expression (≥50% PD-L1) will be limited to a maximum of
                            10 patients

          -  Eastern Cooperative Oncology Group (ECOG, R01-0787) score: 0 to 1

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

          -  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.

        Exclusion Criteria:

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

          -  Patients who must or wish to continue the intake of restricted medications (see
             Section 4.2.2.2) or any drug considered likely to interfere with the safe conduct of
             the trial

          -  Previous enrolment in this trial

          -  Any investigational or anti-tumour treatment, except BI 754091, within 4 weeks or
             within 5 half-life periods (whichever is shorter) prior to the initiation of trial
             treatment.

          -  Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of
             starting study treatment with the exception of alopecia and Grade 2 neuropathy due to
             prior platinum-based therapy

          -  Prior treatment with anti-LAG-3 agents

          -  Patients with Non-small cell lung cancer (NSCLC) that has epidermal growth factor
             receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements

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

          -  Untreated brain metastasis(es) that may be considered active. Patients with previously
             treated brain metastases may participate provided they are stable (i.e., without
             evidence of PD by imaging for at least 4 weeks prior to the first dose of trial
             treatment, and any neurologic symptoms have returned to baseline), and there is no
             evidence of new or enlarging brain metastases.

          -  Inadequate organ function or bone marrow reserve as demonstrated by the laboratory
             values presented in Table 3.3.3: 1.

          -  Any of the following cardiac criteria:

               -  Mean resting corrected QT interval (QTc) >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,
                  multi-gated acquisition scan). 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.

          -  History of pneumonitis within the last 5 years

          -  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 study treatment.

          -  Active autoimmune disease or a documented history of autoimmune disease, except
             vitiligo or resolved childhood asthma/atopy

          -  Active infection requiring systemic treatment (antibacterial, antiviral, or antifungal
             therapy) at start of treatment in this trial

          -  Known history of human immunodeficiency virus infection or an active hepatitis B or C
             virus infection

          -  Interstitial lung disease

          -  Chronic alcohol or drug abuse or any condition that, in the Investigator's opinion,
             makes him/her an unreliable trial subject, unlikely to complete the trial, or unable
             to comply with the protocol procedures.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part I - Maximum-tolerated dose (MTD) of the BI 754111 plus BI 754091 combination
Time Frame:Up to 3 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Part I - Cmax: maximum measured concentration of BI 754111/ BI 754091 in plasma
Time Frame:Up to 1 year and 30 days
Safety Issue:
Description:
Measure:Part I - AUC 0-504: Area under the Concentration Time Curve (AUC 0-504) of BI 754111/ BI 754091 in plasma over the time interval
Time Frame:Up to 504 hours
Safety Issue:
Description:
Measure:Part I - Number of patients experiencing Dose-limiting toxicity (DLTs) from start of treatment until end of treatment (in all cycles)
Time Frame:Up to 1 year and 30 days
Safety Issue:
Description:
Measure:Part I - Objective response (OR) for patients with solid tumours: confirmed complete response (CR) and partial response (PR) according to RECIST Version 1.1 as assessed by the Investigator during the entire treatment period
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Part II - Duration of response is the duration from the date of first documented PR or CR according to RECIST Version 1.1 as assessed by the Investigator to the date of Progression of disease [PD] or death
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Part II - Disease control (CR, PR, or SD according to RECIST Version 1.1) as assessed by the Investigator
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Part II - Progression-free survival (PFS) is the duration from the date of first treatment to the date of PD or death
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Part II - PK parameters: Cmax, and AUC 0-504, will be calculated for BI 754111 and BI 754091 after single and multiple doses of the BI 754111 plus BI 754091 combination treatment
Time Frame:Up to 1 year 30 days
Safety Issue:
Description:
Measure:Part II - Number of patients experiencing DLTs from start of treatment until end of treatment
Time Frame:Up to 1 year
Safety Issue:
Description:

Details

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

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