A Study to Test Different Doses of BI 836880 Combined With Ezabenlimab in Patients With Advanced Non-small Cell Lung Cancer Followed by Other Types of Advanced Solid Tumours

NCT03468426 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 1336-00112017-001378-41
• Study Type: interventional
• Target: 252
• Locations: 12 countries
• Sites: 43

Brief Summary

This study has 2 parts. The first part was open to adults with advanced non-small cell lung cancer. The second part was open also to adults with other types of advanced cancer of the lung, brain, skin, and liver. After early encouraging results, more people with liver cancer can now take part in the study. The participants get a combination of two medicines called BI 836880 and ezabenlimab. BI 836880 is a type of an antibody that blocks new blood vessel formation. New blood vessels are needed by the tumour to continue growing. Ezabenlimab is an antibody that may help the immune system fight cancer (immune checkpoint inhibitor). The purpose of the first part of the study was to find out the highest dose of the BI 836880 that the participants can tolerate in combination with BI 754091. After the best dose of BI 836880 for the combination with ezabenlimab was found, it is used in the second part of the study. The purpose of the second part is to see whether the combination of BI 836880 and BI 754091 is able to make tumours shrink. The participants are in the study as long as they benefit from and can tolerate treatment. During this time, they get infusions of BI 836880 and ezabenlimab every 3 weeks. The doctors also regularly check the general health of the participants.

Conditions

Non-squamous, Non-Small-Cell Lung Cancer; Neoplasms

Outcome Measures

Primary Outcomes (2)

• Part 1 - Number of Patients With Dose Limiting Toxicity (DLT) Within the First Cycle of Treatment

  Number of patients with dose limiting toxicity (DLT) within the first cycle of treatment.

  The first treatment cycle, up to 21 days.

• Part 2 - Objective Response (OR)

  Objective Response (OR) defined as best overall response (Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)) of complete response (CR) or partial response (PR) from first treatment infusion until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anticancer therapy, lost to follow-up, or withdrawal of consent. In case of recurrent glioblastoma (GBM), assessment will be based on RANO (Response Assessment in Neuro-Oncology) criteria.

  Up to 778 days.

Secondary Outcomes (27)

• Part 1 - Adverse Events (AEs)

  Up to 1263 days.

• Part 1 - Drug Related AEs

  Up to 1263 days.

• Part 1 - Drug Related AEs Leading to Dose Reduction or Discontinuation

  Up to 1263 days.

• Part 2 - Adverse Events (AEs)

  Up to 778 days.

• Part 2 - Drug Related AEs

  Up to 778 days.

Study Arms (11)

Part 1 - BI 836880 360 mg

EXPERIMENTAL

Patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who progressed during or after first line platinum-based chemotherapy, received 360 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles.

Drug: BI 836880; Drug: Ezabenlimab

Part 1 - BI 836880 500 mg

EXPERIMENTAL

Patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who progressed during or after first line platinum-based chemotherapy, received 500 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles.

Drug: BI 836880; Drug: Ezabenlimab

Part 1 - BI 836880 720 mg

EXPERIMENTAL

Patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who progressed during or after first line platinum-based chemotherapy, received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles.

Drug: BI 836880; Drug: Ezabenlimab

Part 2 - Cohort A, 2nd line NSCLC

EXPERIMENTAL

Patient with pathologically confirmed locally advanced or metastatic non-squamous NSCLC who progressed during or after check-point inhibitor monotherapy treatment. Patient must also have received treatment with a platinum-based chemotherapy regimen and have progressed or be intolerant, or ineligible, as per applicable local practice. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles.

Drug: BI 836880; Drug: Ezabenlimab

Part 2 - Cohort B, 3rd line NSCLC

EXPERIMENTAL

Patient with pathologically confirmed locally advanced or metastatic non-squamous NSCLC who progressed during or after platinum-based chemotherapy and a check-point inhibitor (CPI) combination treatment as the most recent anticancer treatment. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles.

Drug: BI 836880; Drug: Ezabenlimab

Part 2 - Cohort C, SCLC

EXPERIMENTAL

Patient with pathologically confirmed locally advanced or metastatic Small Cell Lung Cancer (SCLC) with documented intolerance to platinum-based chemotherapy or refractory to platinum-based chemotherapy. Patients who were platinumsensitive must also have received one additional prior line of platinum-based chemotherapy, if eligible, with or without combination with CPI as per applicable local treatment country guidelines. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles.

Drug: BI 836880; Drug: Ezabenlimab

Part 2 - Cohort D, glioblastoma

EXPERIMENTAL

Patient with histologically confirmed recurrent glioblastoma with no more than two previous lines of chemotherapy. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles.

Drug: BI 836880; Drug: Ezabenlimab

Part 2 - Cohort E, Melanoma

EXPERIMENTAL

Patient with histologically confirmed, unresectable, Stage IV metastatic melanoma who progressed during or after CPI based regimen. Patients with a BRAF mutation must have received targeted treatment, or were not eligible, with a BRAF and MEK inhibitor as per applicable local country guidelines. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles.

Drug: BI 836880; Drug: Ezabenlimab

Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma

EXPERIMENTAL

Patient with locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC) who were intolerant or progressed during 1st line sorafenib or lenvatinib treatment. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles.

Drug: BI 836880; Drug: Ezabenlimab

Part 2 - Cohort G, 1st line Hepatocellular Carcinoma (HCC)

EXPERIMENTAL

Patient with locally advanced or metastatic and/or unresectable HCC with no prior systemic treatment. This will be implemented only in countries where this cohort is approved. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles.

Drug: BI 836880; Drug: Ezabenlimab

Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures

EXPERIMENTAL

Patient with locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC) who were intolerant or progressed during 1st line treatment with atezolizumab in combination with bevacizumab. Patients received 720 milligram (mg) BI 836880 and 240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle until progression, unacceptable toxicity, or up to a maximum of 53 cycles.

Drug: BI 836880; Drug: Ezabenlimab

Interventions

BI 836880 DRUG

BI 836880 as an intravenous infusion on day 1 of each 3-week cycle.

Part 1 - BI 836880 360 mg; Part 1 - BI 836880 500 mg; Part 1 - BI 836880 720 mg; Part 2 - Cohort A, 2nd line NSCLC; Part 2 - Cohort B, 3rd line NSCLC; Part 2 - Cohort C, SCLC; Part 2 - Cohort D, glioblastoma; Part 2 - Cohort E, Melanoma; Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma; Part 2 - Cohort G, 1st line Hepatocellular Carcinoma (HCC); Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures

Ezabenlimab DRUG

240 mg Ezabenlimab (BI 754091) as an intravenous infusion on day 1 of each 3-week cycle.

Also known as: BI 754091

Part 1 - BI 836880 360 mg; Part 1 - BI 836880 500 mg; Part 1 - BI 836880 720 mg; Part 2 - Cohort A, 2nd line NSCLC; Part 2 - Cohort B, 3rd line NSCLC; Part 2 - Cohort C, SCLC; Part 2 - Cohort D, glioblastoma; Part 2 - Cohort E, Melanoma; Part 2 - Cohort F, 2nd line Hepatocellular Carcinoma; Part 2 - Cohort G, 1st line Hepatocellular Carcinoma (HCC); Part 2 - Cohort H, 2nd line HCC - atezolizumab in combination with bevacizumab failures

Eligibility Criteria

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

You may qualify if:

• Part 1:
• Of full age (according to local legislation, usually ≥ 18 years) at screening.
• Pathologically confirmed locally advanced or metastatic non-squamous NSCLC with PDL-1 expression available and \>1% by IHC (as defined by the Pembrolizumab companion diagnostic test, determined by appropriate local pathology lab.
• No previous treatment with check-point inhibitor. Or patients with checkpoint inhibitor based treatment as last therapy before entering the trial.
• Documented disease progression or relapse (based on investigator's assessment) during or after completion of at least 2 cycles of platinum-based chemotherapy as first line treatment of Stage IIIB/IV non- squamous NSCLC or for checkpoint inhibitor experienced patients during or after completion of at least 2 cycles of platinum-based chemotherapy and a checkpoint inhibitor treatment (monotherapy or in combination with chemotherapy). This includes patients relapsing within 6 months of completing (neo)adjuvant/curative-intent chemotherapy/CPI or chemoradiotherapy
• At least one target lesion (outside the brain) that can be accurately measured per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 .
• Lesion with a diameter ≥ 2cm assessed by radiologist as suitable for DCE-MRI evaluation (Mandatory in Part 1, optional in Part 2)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Life expectancy ≥ 3 months after start of the treatment in the opinion of the investigator
• Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or CTCAE grade 1, except for alopecia (any grade), sensory peripheral neuropathy , must be ≤ CTCAE grade 2 or considered not clinically significant.
• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
• Availability and willingness to provide a fresh tumour tissue sample obtained at baseline, and after 2 cycles of treatment
• Adequate organ function defined as all of the following (all screening labs should be performed at local lab within 10 days prior to treatment initiation)
• Male or female patients. Women of childbearing potential (WOCBP)1 and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly, starting with the screening visit and through 6 months after the last dose of BI 836880 and BI 754091 treatment, respectively. A list of contraception methods meeting these criteria is provided in the patient information Note: Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to taking study medication during the screening period. At the following visits according to the flowchart a urine and/or serum pregnancy test is required. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible.
• Part 2:
• Of full age (according to local legislation, usually ≥ 18 years) at screening

You may not qualify if:

• Part 1:
• Known hypersensitivity to the trial drugs or their excipients or risk of allergic of anaphylactic reaction to drug product according to Investigator judgement (e.g. patient with history of anaphylactic reaction or autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids, or the equivalent of \</= 10 mg/day prednisone).
• Known immunodeficiency virus infection or an active hepatitis B or C virus infection.
• History of severe hypersensitivity reactions to other mAbs.
• Immunosuppressive corticosteroid doses (\> 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of trial medication.
• Current or prior treatment with any systemic anti-cancer therapy either within 28 days or a minimum of 5 half-lives, whichever is shorter before start of treatment.
• Serious concomitant disease, especially those affecting compliance with trial requirements or which are considered relevant for the evaluation of the endpoints of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastrointestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the investigator would make the patient inappropriate for entry into the trial.
• Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment, or planned surgical procedures during the trial period.
• Patients with personal or family history of QT prolongation and/or long QT syndrome, or prolonged QTcF at baseline (\> 480 ms).
• Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure \> NYHA II).
• Uncontrolled hypertension defined as: Blood pressure in rested and relaxed condition \>= 140 mmHg, systolic or \>= 90 mmHg diastolic (with or without medication), measured according to Appendix 10.2.
• LVEF \< 50%
• History of severe hemorrhagic or thromboembolic event in the past 12 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis).
• Known inherited predisposition to bleeding or to thrombosis in the opinion of the investigator.
• Patient with brain metastases that are symptomatic and/or require therapy.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (43)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Royal North Shore Hospital-St Leonards-20807

St Leonards, New South Wales, 2065, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Peninsula & South Eastern Oncology Group

Frankston, Victoria, 3199, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

CTR Georges-François Leclerc

Dijon, 21079, France

Location

HOP Timone

Marseille, 13385, France

Location

INS Curie

Paris, 75005, France

Location

CTR Eugène Marquis

Rennes, 35042, France

Location

HOP Nord Laennec

Saint-Herblain, 44800, France

Location

HOP Civil

Strasbourg, 67091, France

Location

Universitätsklinikum Augsburg

Augsburg, 86156, Germany

Location

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, 60528, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

University Clinical Center, Gdansk

Gdansk, 80-952, Poland

Location

Mandziuk Slawomir Specialist Medical Practice

Lublin, 20-093, Poland

Location

European Health Center Otwock

Otwock, 05-462, Poland

Location

MED POLONIA SP Z O O, Clinical Trials Department,Poznan

Poznan, 60-693, Poland

Location

Dom Lekarski S.A.

Szczecin, 70-784, Poland

Location

JSC "Group of Companies "Medsi"

Moscow, 125284, Russia

Location

SBHI "Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncological)"

Saint Petersburg, 197758, Russia

Location

State Budget Healthcare Institution "Volgograd Regional Clinical Oncology Dispensary"

Volgograd, 400138, Russia

Location

Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hospital Universitari Vall D Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Clinico Universitario De Valencia

Valencia, 46010, Spain

Location

NCKUH

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council

Dnipropetrovks, 49102, Ukraine

Location

Kyiv City Clinical Oncological Center

Kyiv, 3115, Ukraine

Location

Medical and Preventive Treatment Inst. Volyn Regional, Lutsk

Lutsk, 43018, Ukraine

Location

Vinnytsia Regional Clinical Oncological Dispensary

Vinnytsia, 21029, Ukraine

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

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: March 8, 2018
• First Posted: March 16, 2018
• Study Start: July 5, 2018
• Primary Completion: July 31, 2024
• Study Completion: September 12, 2024
• Last Updated: November 10, 2025
• Results First Posted: November 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); AU (4); HK (1); US (6); DE (5); KR (3); FR (6); PL (5); RU (3); ES (3); TW (2); UA (4)