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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.

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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03156114
Recruitment Status : Active, not recruiting
First Posted : May 17, 2017
Last Update Posted : November 16, 2022
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:

This is a study in adults with advanced solid tumors including non-small cell lung cancer.

The study tests the combination of two medicines called BI 754111 and BI 754091 that may help the immune system to fight the cancer. Such medicines are called immune checkpoint inhibitors.

The study has two parts. In the first part, doctors want to find out the highest dose of 2 medicines that people with solid tumors can tolerate. This dose is then used for the second part of the study.

In the second part, the combination of the two medicines is tested in patients with non-small cell lung cancer and other types of solid cancer. These patients had gotten treatment with anti-PD-1 or anti-PD-L1 medicines but their tumors have come back. The doctors check whether the combination of BI 754111 and BI 754091 makes tumors shrink.

Both medicines are given as an infusion into the vein every 3 weeks. If there is benefit for the patients and if they can tolerate it, the treatment is given for maximum of 1 year. During the entire study doctors will regularly check the health of the patients.

Condition or disease Intervention/treatment Phase
Neoplasms Carcinoma, Non-Small-Cell Lung Drug: BI 754111 Drug: BI 754091 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 172 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: 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
Actual Study Start Date : June 13, 2017
Estimated Primary Completion Date : June 15, 2023
Estimated Study Completion Date : June 15, 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Part I - Dose--Escalation Drug: BI 754111
Day 1 of 3 week cycle

Drug: BI 754091
Day 1 of 3 week cycle

Experimental: Part II - Dose-Expansion Drug: BI 754111
Day 1 of 3 week cycle

Drug: BI 754091
Day 1 of 3 week cycle

Primary Outcome Measures :
  1. Part I - Maximum-tolerated dose (MTD) of the BI 754111 plus BI 754091 combination [ Time Frame: Up to 3 weeks ]
  2. Part I - Number of patients experiencing Dose-limiting toxicity (DLTs) during the combination Maximum-tolerated dose (MTD) evaluation period (first cycle of BI 754111 plus BI 754091 combination therapy) in patients with solid tumours [ Time Frame: Up to 3 weeks ]
  3. Part II - Objective response (OR) - confirmed complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 as assessed by the Investigator during the entire treatment [ Time Frame: Up to 1 year ]

Secondary Outcome Measures :
  1. Part I - Cmax: maximum measured concentration of BI 754111/ BI 754091 in plasma [ Time Frame: Up to 1 year and 30 days ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. Part II - Disease control (CR, PR, or stable disease (SD) according to RECIST Version 1.1) as assessed by the Investigator [ Time Frame: Up to 1 year ]
  7. 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 ]
  8. Part II - Number of patients experiencing DLTs from start of treatment until end of treatment [ Time Frame: Up to 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 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: Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours of one of the following types:

      • 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 4 months 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 Metastatic colorectal Cancer (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 epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild type (only applicable to patients with non-squamous NSCLC)
        • Regardless of 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 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-Lymphocyte-activation gene 3 (LAG-3) agents
  • Patients with NSCLC that has EGFR mutations or ALK rearrangements (only applicable to patients with non-squamous NSCLC).
  • 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.

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): NCT03156114

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United States, Florida
University of Miami
Miami, Florida, United States, 33136
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
United States, New Jersey
John Theurer Cancer Center
Hackensack, New Jersey, United States, 07601
United States, Oklahoma
Stephenson Cancer Center
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37203
United States, Wisconsin
Froedtert and The Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Alberta
Cross Cancer Institute (University of Alberta)
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 1Z9
BioVirtus Research Site Sp. z o.o.
Józefów, Poland, 05-410
Onco.Cent. - Instit. of Maria Sklodowskiej-Curie
Warszawa, Poland, 02-781
Hospital Universitari Dexeus
Barcelona, Spain, 08028
Hospital General Universitario Gregorio Marañón
Madrid, Spain, 28007
Hospital Universitario HM Sanchinarro
Madrid, Spain, 28050
Hospital Politècnic La Fe
Valencia, Spain, 46026
United Kingdom
Sarah Cannon Research Institute
London, United Kingdom, W1G 6AD
Sponsors and Collaborators
Boehringer Ingelheim
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03156114    
Other Study ID Numbers: 1381-0002
2017-005042-29 ( EudraCT Number )
First Posted: May 17, 2017    Key Record Dates
Last Update Posted: November 16, 2022
Last Verified: November 2022
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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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases