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 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 1381-00022017-005042-29
• Study Type: interventional
• Target: 172
• Locations: 5 countries
• Sites: 15

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.

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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)

  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

  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

  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

  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)

  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.

Study Arms (11)

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).

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).

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).

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).

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).

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).

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).

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.

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).

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.

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.

Drug: Ezabenlimab; Drug: BI 754111

Interventions

Ezabenlimab DRUG

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; 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 754111 DRUG

Different dosages of BI 754111 given as an intravenous infusion on day 1 of 21-day cycles (q3w).

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (15)

University of Miami

Miami, Florida, 33136, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Froedtert and The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Cross Cancer Institute (University of Alberta)

Edmonton, Alberta, T6G 1Z2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z9, Canada

Location

BioVirtus Research Site Sp. z o.o.

Józefów, 05-410, Poland

Location

Oncology Center-Maria Sklodowska-Curie Institute

Warsaw, 02-781, Poland

Location

Hospital Universitari Dexeus

Barcelona, 08028, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Politècnic La Fe

Valencia, 46026, Spain

Location

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35756842 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Boehringer Ingelheim , Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2017
• First Posted: May 17, 2017
• Study Start: June 13, 2017
• Primary Completion: March 9, 2023
• Study Completion: June 6, 2023
• Last Updated: January 26, 2026
• Results First Posted: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); GB (1); CA (2); ES (4); PL (2)