NeoplasmsPhase 1NCT03156114
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.
A Phase 1 study testing Ezabenlimab and BI 754111 in people with Neoplasms and Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 15 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Ezabenlimab and BI 754111
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 172 participants
- Where
- 15 sitesin 5 countries
- Study dates
- 13 Jun 2017to 6 Jun 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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-Lymphocyte-activation gene 3 (LAG-3) agents
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- 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.
Trial locations and contacts
15 sites in 5 countries.
15 sites in 5 countries
United States6 sites
John Theurer Cancer Center
Hackensack, New Jersey, 07601
University of Miami
Miami, Florida, 33136
Froedtert and The Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Florida Cancer Specialists
Sarasota, Florida, 34232
Spain4 sites
Hospital Universitari Dexeus
Barcelona, 08028
Hospital General Universitario Gregorio Marañón
Madrid, 28007
Hospital Universitario HM Sanchinarro
Madrid, 28050
Hospital Politècnic La Fe
Valencia, 46026
Canada2 sites
Cross Cancer Institute (University of Alberta)
Edmonton, Alberta, T6G 1Z2
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 1Z9
Poland2 sites
BioVirtus Research Site Sp. z o.o.
Józefów, 05-410
Oncology Center-Maria Sklodowska-Curie Institute
Warsaw, 02-781
About this study
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
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.
Read more
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.
- Conditions
- Neoplasms, Carcinoma, Non-Small-Cell Lung
- Being tested
- Ezabenlimab, BI 754111
- Medical subject headings
- Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EzabenlimabDrug
240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w)
BI 754111Drug
Different dosages of BI 754111 given as an intravenous infusion on day 1 of 21-day cycles (q3w).
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation cohort: BI 754111 4 mg + 240 mg ezabenlimab | Experimental | 4 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). Receives: Drug: Ezabenlimab; Drug: BI 754111 |
| Dose escalation cohort: BI 754111 20 mg + 240 mg ezabenlimab | Experimental | 20 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). Receives: Drug: Ezabenlimab; Drug: BI 754111 |
| Dose escalation cohort: BI 754111 80 mg + 240 mg ezabenlimab | Experimental | 80 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). Receives: Drug: Ezabenlimab; Drug: BI 754111 |
| Dose escalation cohort: BI 754111 200 mg + 240 mg ezabenlimab | Experimental | 200 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). Receives: Drug: Ezabenlimab; Drug: BI 754111 |
| Dose escalation cohort: BI 754111 400 mg + 240 mg ezabenlimab | Experimental | 400 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). Receives: Drug: Ezabenlimab; Drug: BI 754111 |
| Dose escalation cohort: BI 754111 600 mg + 240 mg ezabenlimab | Experimental | 600 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). Receives: Drug: Ezabenlimab; Drug: BI 754111 |
| Dose escalation cohort: BI 754111 800 mg + 240 mg ezabenlimab | Experimental | 800 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). Receives: Drug: Ezabenlimab; Drug: BI 754111 |
| Dose-Expansion Cohort G | Experimental | 600 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w) in patients with 2nd and 3rd line Non-small cell lung cancer (NSCLC) who progressed on anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) treatment. Receives: Drug: Ezabenlimab; Drug: BI 754111 |
| Dose-Expansion Cohort H | Experimental | 600 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w) in ≥2nd line microsatellite stable anti-PD-1 and anti-PD-L1 treatment-naïve metastatic colorectal cancer (mCRC). Receives: Drug: Ezabenlimab; Drug: BI 754111 |
| Dose-Expansion Cohort I | Experimental | 600 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w) in patients with any solid tumour with high tumour mutational burden (TMB) and/or microsatellite instability high (MSI-H) and/or DNA mismatch repair deficient solid tumours who have received 1 prior anti-PD-1 or anti-PD-L1 treatment regimen. Receives: Drug: Ezabenlimab; Drug: BI 754111 |
| Dose-Expansion Cohort J | Experimental | 600 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w) patients with 1st line epidermal growth factor receptor (EGFR) wildtype (WT) and anaplastic lymphoma kinase (ALK) wildtype NSCLC. Patients may have any level of PD-L1 expression, but only a maximum of 10 patients with PD-L1 high expression (≥50% PD-L1) were enrolled. Receives: Drug: Ezabenlimab; Drug: BI 754111 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation: Maximum-tolerated Dose (MTD) of the BI 754111 Plus Ezabenlimab Combination
The MTD is defined as the highest dose with less than 25% risk of the true Dose-limiting toxicity (DLT) rate being above 33%. DLTs include:
Haematologic toxicities:
- Any Grade 5 toxicity
- Neutropenia ≥ Grade 4 for >5 days
- Any duration febrile neutropenia
- Grade 4 thrombocytopenia or Grade 3 with bleeding/platelet transfusion need
- Unexplained Grade 4 anaemia.
Non-haematological toxicities:
- Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >3x Upper limit of normal (ULN) and total bilirubin >2x ULN without cholestasis signs
- ≥Grade 4 AST or ALT of any duration
- Any ≥Grade 3 non-haematologic toxicity with exceptions
- Any Grade 4 or 5 adverse event (AE)
- Any Grade 2 pneumonitis
- Any Grade 2 uveitis, eye pain, or blurred vision not improving to Grade 1 within 2 weeks or requiring systemic treatment
- Any ≥ Grade 2 toxicity causing inability to administer BI 754091 on Cycle 2 Day 1.
Measured: First treatment cycle, the first 21 days following the start of trial medication.
Dose Escalation: Number of Patients Experiencing DLTs During the Combination MTD Evaluation Period
Number of patients experiencing DLTs during the combination MTD evaluation period (first cycle of BI 754111 plus ezabenlimab combination therapy) in patients with solid tumours.
Measured: First treatment cycle, the first 21 days following the start of trial medication.
Dose Expansion: Number of Patients With Objective Response (OR) - Confirmed Complete Response (CR) and Partial Response (PR)
Dose expansion: Number of patients with 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.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period), up to 818 days.
Secondary outcomes (14)
Dose Escalation: Number of Patients With Objective Response (OR) - Confirmed Complete Response (CR) and Partial Response (PR)
Dose escalation: Number of patients with objective response (OR) - confirmed complete response (CR) and partial response (PR) according to RECIST Version 1.1 as assessed by the Investigator during the entire treatment.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period), up to 1286 days.
Dose Escalation: Number of Patients Experiencing DLTs
Dose escalation: Number of patients experiencing DLTs from start of treatment until end of treatment (in all cycles).
Measured: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period), up to 1286 days.
Dose Expansion: Duration of Response
Duration of response is measured from the time measurements criteria are met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease (PD) is objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started).
Measured: From the date of objective response until first date that recurrent or PD has been documented, up to 100 weeks.
Dose Expansion: Percentage of Patients With Disease Control
Dose expansion: Percentage of patients with disease control (CR, PR, or stable disease (SD) according to RECIST Version 1.1) as assessed by the Investigator.
Measured: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period), up to 818 days.
Dose Expansion: Progression-free Survival (PFS)
Dose expansion: Progression-free survival (PFS) is defined as time from first drug intake until disease progression or death from any cause, whichever occurs earlier. The date of progression will be based on the Investigator assessment according to RECIST 1.1.
For patients with 'event' as an outcome for PFS:
- PFS [days] = date of outcome - date of start of treatment + 1
For patients with 'censored' as an outcome for PFS:
- PFS (censored) [days] = date of outcome - date of start of treatment + 1
Days were converted into months for reporting.
Measured: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period), up to 818 days.
Dose Expansion: Number of Patients Experiencing DLTs
Dose expansion: Number of patients experiencing DLTs from start of treatment until end of treatment.
Measured: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period), up to 818 days.
Dose Escalation: AUC0-504: Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours
Dose escalation: AUC0-504: area under the concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours.
Measured: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the first treatment cycle.
Dose Escalation: AUC0-504 Steady State: Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours
Dose escalation: AUC0-504 steady state: area under the concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours at steady state.
Measured: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the fourth treatment cycle.
Dose Escalation: AUC0-504: Area Under the Concentration-time Curve of BI 754111 in Plasma Over the Time Interval From 0 to 504 Hours
Dose escalation: AUC0-504: area under the concentration-time curve of BI 754111 in plasma over the time interval from 0 to 504 hours.
Measured: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the first treatment cycle.
Dose Escalation: AUC0-504 Steady State: Area Under the Concentration-time Curve of BI 754111 in Plasma Over the Time Interval From 0 to 504 Hours
Dose escalation: AUC0-504 steady state: area under the concentration-time curve of BI 754111 in plasma over the time interval from 0 to 504 hours at steady state.
Measured: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the fourth treatment cycle.
Dose Escalation: Cmax: Maximum Measured Concentration of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours
Dose escalation: Cmax: maximum measured concentration of ezabenlimab in plasma over the time interval from 0 to 504 hours.
Measured: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the first treatment cycle.
Dose Escalation: Cmax Steady State: Maximum Measured Concentration of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours
Dose escalation: Cmax steady state: maximum measured concentration of ezabenlimab in plasma over the time interval from 0 to 504 hours at steady state.
Measured: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the fourth treatment cycle.
Dose Escalation: Cmax: Maximum Measured Concentration of BI 754111 in Plasma Over the Time Interval From 0 to 504 Hours
Dose escalation: Cmax: maximum measured concentration of BI 754111 in plasma over the time interval from 0 to 504 hours.
Measured: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the first treatment cycle.
Dose Escalation: Cmax Steady State: Maximum Measured Concentration of BI 754111 in Plasma Over the Time Interval From 0 to 504 Hours
Dose escalation: Cmax steady state: maximum measured concentration of BI 754111 in plasma over the time interval from 0 to 504 hours at steady state.
Measured: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the fourth treatment cycle.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2017
- Study start13 Jun 2017
- Primary completion9 Mar 2023
- Study completion6 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 172 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03156114
- Sponsor's protocol ID
- 1381-0002
- Other IDs
- 2017-005042-29, 2017
- Status last verified
- Jan 2026
- First submitted
- 15 May 2017
- Last updated
- 26 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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
Publications
Zettl M, Wurm M, Schaaf O, Mostbock S, Tirapu I, Apfler I, Lorenz IC, Frego L, Kenny C, Thibodeau M, Oquendo Cifuentes E, Reschke M, Moll J, Kraut N, Vogt A, Sedgwick JD, Waizenegger IC. Combination of two novel blocking antibodies, anti-PD-1 antibody ezabenlimab (BI 754091) and anti-LAG-3 antibody BI 754111, leads to increased immune cell responses. Oncoimmunology. 2022 Jun 16;11(1):2080328. doi: 10.1080/2162402X.2022.2080328. eCollection 2022.
PubMed 35756842
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03156114
- Acronym / sponsor ID
- 1381-0002
- Conditions
- Neoplasms, Carcinoma, Non-Small-Cell Lung
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 172 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 13 Jun 2017 (actual)
- Primary completion
- 9 Mar 2023 (actual)
- Study completion
- 6 Jun 2023 (actual)
- First posted
- 17 May 2017 (actual)
- Results
- Posted 26 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Dose escalation cohort: BI 754111 4 mg + 240 mg ezabenlimab | Experimental | Drug: Ezabenlimab, Drug: BI 7541114 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). |
| Dose escalation cohort: BI 754111 20 mg + 240 mg ezabenlimab | Experimental | Drug: Ezabenlimab, Drug: BI 75411120 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). |
| Dose escalation cohort: BI 754111 80 mg + 240 mg ezabenlimab | Experimental | Drug: Ezabenlimab, Drug: BI 75411180 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). |
| Dose escalation cohort: BI 754111 200 mg + 240 mg ezabenlimab | Experimental | Drug: Ezabenlimab, Drug: BI 754111200 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). |
| Dose escalation cohort: BI 754111 400 mg + 240 mg ezabenlimab | Experimental | Drug: Ezabenlimab, Drug: BI 754111400 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). |
| Dose escalation cohort: BI 754111 600 mg + 240 mg ezabenlimab | Experimental | Drug: Ezabenlimab, Drug: BI 754111600 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). |
| Dose escalation cohort: BI 754111 800 mg + 240 mg ezabenlimab | Experimental | Drug: Ezabenlimab, Drug: BI 754111800 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w). |
| Dose-Expansion Cohort G | Experimental | Drug: Ezabenlimab, Drug: BI 754111600 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w) in patients with 2nd and 3rd line Non-small cell lung cancer (NSCLC) who progressed on anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) treatment. |
| Dose-Expansion Cohort H | Experimental | Drug: Ezabenlimab, Drug: BI 754111600 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w) in ≥2nd line microsatellite stable anti-PD-1 and anti-PD-L1 treatment-naïve metastatic colorectal cancer (mCRC). |
| Dose-Expansion Cohort I | Experimental | Drug: Ezabenlimab, Drug: BI 754111600 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w) in patients with any solid tumour with high tumour mutational burden (TMB) and/or microsatellite instability high (MSI-H) and/or DNA mismatch repair deficient solid tumours who have received 1 prior anti-PD-1 or anti-PD-L1 treatment regimen. |
| Dose-Expansion Cohort J | Experimental | Drug: Ezabenlimab, Drug: BI 754111600 milligram (mg) BI 754111 and 240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w) patients with 1st line epidermal growth factor receptor (EGFR) wildtype (WT) and anaplastic lymphoma kinase (ALK) wildtype NSCLC. Patients may have any level of PD-L1 expression, but only a maximum of 10 patients with PD-L1 high expression (≥50% PD-L1) were enrolled. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- 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)
- Part II (dose expansion):
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ezabenlimab240 mg ezabenlimab given as an intravenous infusion on day 1 of 21-day cycles (q3w) | Drug | Dose escalation cohort: BI 754111 20 mg + 240 mg ezabenlimab, Dose escalation cohort: BI 754111 200 mg + 240 mg ezabenlimab, Dose escalation cohort: BI 754111 4 mg + 240 mg ezabenlimab, Dose escalation cohort: BI 754111 400 mg + 240 mg ezabenlimab, Dose escalation cohort: BI 754111 600 mg + 240 mg ezabenlimab, Dose escalation cohort: BI 754111 80 mg + 240 mg ezabenlimab, Dose escalation cohort: BI 754111 800 mg + 240 mg ezabenlimab, Dose-Expansion Cohort G, Dose-Expansion Cohort H, Dose-Expansion Cohort I, Dose-Expansion Cohort J |
| BI 754111Different dosages of BI 754111 given as an intravenous infusion on day 1 of 21-day cycles (q3w). | Drug | Dose escalation cohort: BI 754111 20 mg + 240 mg ezabenlimab, Dose escalation cohort: BI 754111 200 mg + 240 mg ezabenlimab, Dose escalation cohort: BI 754111 4 mg + 240 mg ezabenlimab, Dose escalation cohort: BI 754111 400 mg + 240 mg ezabenlimab, Dose escalation cohort: BI 754111 600 mg + 240 mg ezabenlimab, Dose escalation cohort: BI 754111 80 mg + 240 mg ezabenlimab, Dose escalation cohort: BI 754111 800 mg + 240 mg ezabenlimab, Dose-Expansion Cohort G, Dose-Expansion Cohort H, Dose-Expansion Cohort I, Dose-Expansion Cohort J |
Primary outcome
Dose Escalation: Maximum-tolerated Dose (MTD) of the BI 754111 Plus Ezabenlimab Combination
Time frame: First treatment cycle, the first 21 days following the start of trial medication.
The MTD is defined as the highest dose with less than 25% risk of the true Dose-limiting toxicity (DLT) rate being above 33%. DLTs include: Haematologic toxicities: * Any Grade 5 toxicity * Neutropenia ≥ Grade 4 for >5 days * Any duration febrile neutropenia * Grade 4 thrombocytopenia or Grade 3 with bleeding/platelet transfusion need * Unexplained Grade 4 anaemia. Non-haematological toxicities: * Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >3x Upper limit of normal (ULN) and total bilirubin >2x ULN without cholestasis signs * ≥Grade 4 AST or ALT of any duration * Any ≥Grade 3 non-haematologic toxicity with exceptions * Any Grade 4 or 5 adverse event (AE) * Any Grade 2 pneumonitis * Any Grade 2 uveitis, eye pain, or blurred vision not improving to Grade 1 within 2 weeks or requiring systemic treatment * Any ≥ Grade 2 toxicity causing inability to administer BI 754091 on Cycle 2 Day 1.
Dose Escalation: Number of Patients Experiencing DLTs During the Combination MTD Evaluation Period
Time frame: First treatment cycle, the first 21 days following the start of trial medication.
Number of patients experiencing DLTs during the combination MTD evaluation period (first cycle of BI 754111 plus ezabenlimab combination therapy) in patients with solid tumours.
Dose Expansion: Number of Patients With Objective Response (OR) - Confirmed Complete Response (CR) and Partial Response (PR)
Time frame: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period), up to 818 days.
Dose expansion: Number of patients with 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. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
14 secondary outcomes
Dose Escalation: Number of Patients With Objective Response (OR) - Confirmed Complete Response (CR) and Partial Response (PR)
Time frame: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period), up to 1286 days.
Dose Escalation: Number of Patients Experiencing DLTs
Time frame: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period), up to 1286 days.
Dose Expansion: Duration of Response
Time frame: From the date of objective response until first date that recurrent or PD has been documented, up to 100 weeks.
Dose Expansion: Percentage of Patients With Disease Control
Time frame: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period), up to 818 days.
Dose Expansion: Progression-free Survival (PFS)
Time frame: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period), up to 818 days.
Dose Expansion: Number of Patients Experiencing DLTs
Time frame: From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period), up to 818 days.
Dose Escalation: AUC0-504: Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours
Time frame: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the first treatment cycle.
Dose Escalation: AUC0-504 Steady State: Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours
Time frame: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the fourth treatment cycle.
Dose Escalation: AUC0-504: Area Under the Concentration-time Curve of BI 754111 in Plasma Over the Time Interval From 0 to 504 Hours
Time frame: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the first treatment cycle.
Dose Escalation: AUC0-504 Steady State: Area Under the Concentration-time Curve of BI 754111 in Plasma Over the Time Interval From 0 to 504 Hours
Time frame: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the fourth treatment cycle.
Dose Escalation: Cmax: Maximum Measured Concentration of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours
Time frame: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the first treatment cycle.
Dose Escalation: Cmax Steady State: Maximum Measured Concentration of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours
Time frame: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the fourth treatment cycle.
Dose Escalation: Cmax: Maximum Measured Concentration of BI 754111 in Plasma Over the Time Interval From 0 to 504 Hours
Time frame: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the first treatment cycle.
Dose Escalation: Cmax Steady State: Maximum Measured Concentration of BI 754111 in Plasma Over the Time Interval From 0 to 504 Hours
Time frame: Within 1 hour before and 1, 4, 7, 24, 72, 168, 336 and 504 hours following the start of infusion in the fourth treatment cycle.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35756842Zettl M, Wurm M, Schaaf O, Mostbock S, Tirapu I, Apfler I, Lorenz IC, Frego L, Kenny C, Thibodeau M, Oquendo Cifuentes E, Reschke M, Moll J, Kraut N, Vogt A, Sedgwick JD, Waizenegger IC. Combination of two novel blocking antibodies, anti-PD-1 antibody ezabenlimab (BI 754091) and anti-LAG-3 antibody BI 754111, leads to increased immune cell responses. Oncoimmunology. 2022 Jun 16;11(1):2080328. doi: 10.1080/2162402X.2022.2080328. eCollection 2022.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ezabenlimab and BI 754111 in people with Neoplasms and Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 15 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Spain, Canada, Poland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Escalation: Maximum-tolerated Dose (MTD) of the BI 754111 Plus Ezabenlimab Combination (time frame: First treatment cycle, the first 21 days following the start of trial medication.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03156114, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2026.