NeoplasmsPhase 1NCT03972150
A Study to Find the Best Dose of BI 836880 Alone and in Combination With BI 754091 in Japanese Patients With Different Types of Advanced Cancer
A Phase 1 study testing BI 836880 and BI 754091 in people with Neoplasms, run by Boehringer Ingelheim at 2 sites in Japan.
Trial summary
The primary objective of this trial is: Part I To determine Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BI 836880 monotherapy Part II To determine MTD and/or RP2D of the combination therapy of BI 836880 and BI 754091 The secondary objectives are: Part I To document the safety and… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neoplasms
- What is being tested?
- BI 836880 and BI 754091
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesJapan
- Study dates
- 12 Jun 2019to 28 Mar 2022
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Of legal age (according to local legislation) at screening. No upper limit.
- Signed and dated written informed consent in accordance with International Council on Harmonisation (ICH) Good Clinical Practice (GCP) and local legislation prior to admission to the trial.
- 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 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 study treatment. A list of contraception methods meeting these criteria is provided in the patient information. The requirement of contraception does not apply to women of no childbearing potential and men not able to father a child, but they must have an evidence of such at screening.
- Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours (any type). Measurable lesion not mandatory for participation in this trial.
- Patients with no therapy of proven efficacy, or who are not amenable to standard therapies.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
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- Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or Common Terminology Criteria for Adverse Events (CTCAE) grade 1, except for alopecia (any grade), sensory peripheral neuropathy, must be ≤ CTCAE grade 2 or considered not clinically significant.
- Adequate organ function.
- Further inclusion criteria apply.
Who cannot join
- 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 history of human immunodeficiency virus (HIV) infection. Test results obtained in routine diagnostics are acceptable if done within 14 days before the informed consent date.
- Any of the following laboratory evidence of hepatitis virus infection.
- Positive results of hepatitis B surface (HBs) antigen
- Presence of hepatitis B core (HBc) antibody together with hepatitis virus B (HBV) Deoxyribonucleic acid (DNA)
- Presence of hepatitis virus C (HCV) Ribonucleic acid (RNA) Test results obtained in routine diagnostics are acceptable if done within 14 days before the informed consent date.
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- History of severe known 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.
- Any investigational or anti-tumour treatment within 4 weeks or 5 half-life periods (whichever is shorter) prior to the initiation of trial 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 (Corrected QT interval by Fridericia) at screening (>470 ms).
- Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure >NYHA [New York Heart Association] class II).
- Uncontrolled hypertension is defined as follows: Blood pressure in rested and relaxed condition ≥140 mmHg, systolic or ≥90 mmHg diastolic (with or without medication)
- Left Ventricular Ejection Fraction (LVEF) <50% measured locally by echocardiography
- History of severe haemorrhagic 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.
- 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 progressive disease (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
- Patients who require full-dose anticoagulation (according to local guidelines). No Vitamin K antagonist and other anticoagulation allowed; Low Molecular Weight Heparin (LMWH) allowed only for prevention not for curative treatment.
- History (including current) of interstitial lung disease or pneumonitis within the last 5 years.
- Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial
- Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled. (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator's opinion, makes the patient an unreliable trial participant).
- Patients who were previously treated in this trial.
- Patients with haematological malignancies.
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial. Female patients of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to taking study medication. 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. Women who are nursing can be enrolled if they stop nursing. In this case, the patient cannot resume nursing even after discontinuation of study treatment.
- Further exclusion criteria apply.
Trial locations and contacts
2 sites in 1 country.
Japan2 sites
Shizuoka Cancer Center
Shizuoka, Sunto-gun, 411-8777
National Cancer Center Hospital
Tokyo, Chuo-ku, 104-0045
About this study
Official title: An Open Label, Phase I Study of BI 836880 Monotherapy and Combination Therapy of BI 836880 and BI 754091 in Japanese Patients With Advanced Solid Tumours
The primary objective of this trial is:
Part I
- To determine Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BI 836880 monotherapy Part II
- To determine MTD and/or RP2D of the combination therapy of BI 836880 and BI 754091
The secondary objectives are:
Part I
- To document the safety and tolerability, and characterise pharmacokinetics (PK) of BI 836880 as monotherapy Part II
- To document the safety and tolerability, and characterise PK of the combination therapy of BI 836880 and BI 754091
- Conditions
- Neoplasms
- Being tested
- BI 836880, BI 754091
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 836880Drug
Solution for infusion
BI 754091Drug
Solution for infusion
| Study group | Role | What they receive |
|---|---|---|
| Part 1: 360 mg BI 836880 | Experimental | Patients with advanced solid tumors were administered intravenously (i.v.) 360 milligram (mg) of BI 836880 solution for infusion on Day 1 of each 3-week cycle until progressive disease, unacceptable toxicity, or other withdrawal criteria were met (Part 1). Receives: Drug: BI 836880 |
| Part 1: 720 mg BI 836880 | Experimental | Patients with advanced solid tumors were administered intravenously (i. v.) 720 milligram (mg) of BI 836880 solution for infusion on Day 1 of each 3-week cycle until progressive disease, unacceptable toxicity, or other withdrawal criteria were met (Part 1). Receives: Drug: BI 836880 |
| Part 2: 120 mg of BI 836880/ 240 mg Ezabenlimab | Experimental | Patients with advanced solid tumors were administered intravenously (i. v.) 120 milligram (mg) of BI 836880 solution for infusion and 240 mg Ezabenlimab (BI 754091) solution for infusion on Day 1 of each 3-week cycle until progressive disease, unacceptable toxicity, or other withdrawal criteria were met (Part 2). Part 2 commenced after completion of Part 1. Receives: Drug: BI 836880; Drug: BI 754091 |
| Part 2: 360 mg BI 836880/ 240 mg Ezabenlimab | Experimental | Patients with advanced solid tumors were administered intravenously (i. v.) 360 milligram (mg) of BI 836880 solution for infusion and 240 mg Ezabenlimab (BI 754091) solution for infusion on Day 1 of each 3-week cycle until progressive disease, unacceptable toxicity, or other withdrawal criteria were met (Part 2). Part 2 commenced after completion of Part 1. Receives: Drug: BI 836880; Drug: BI 754091 |
| Part 2: 720 mg BI 836880 / 240 mg Ezabenlimab | Experimental | Patients with advanced solid tumors were administered intravenously (i. v.) 720 milligram (mg) of BI 836880 solution for infusion and 240 mg Ezabenlimab (BI 754091) solution for infusion on Day 1 of each 3-week cycle until progressive disease, unacceptable toxicity, or other withdrawal criteria were met (Part 2). Part 2 commenced after completion of Part 1. Receives: Drug: BI 836880; Drug: BI 754091 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of BI 836880 Monotherapy and Combination Therapy of BI 836880 and BI754091
Maximum tolerated dose (MTD) of BI 836880 monotherapy (Part 1) and combination therapy of BI 836880 and BI75409 (Part 2). The MTD was defined as the highest dose with less than 25% risk of the true dose-limiting toxicity (DLT) rate being equal or above 0.33 (EWOC criterion) during the MTD evaluation period. The analysis of the MTD was based on a Bayesian logistic regression model (BLRM) guided by the escalation with overdose control principle. The estimated probability of a DLT at each dose level from the model was summarized using the following intervals:
Underdosing: [0.00, 0.16) Targeted toxicity: [0.16, 0.33) Over toxicity: [0.33, 1.00]
Measured: First treatment cycle, the first 21 days following the start of trial medication.
Number of Participants With Dose-limiting Toxicity (DLT) During the First Treatment Cycle
Number of participants with DLT occurring during the first treatment cycle. DLT was defined as any of the following adverse events related to the treatment: Haematologic toxicities: -Any Grade 5 toxicity,-Neutropenia Grade 4 lasting for >7 days,-Grade ≥3 documented infection with neutropenia,-Febrile neutropenia (absolute neutrophil count <1.0 X 109 cells/L and fever ≥38.5C or a sustained temperature of ≥38.0 Centigrade (C) for more than 1 hour),-Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding,-Thrombocytopenia of any Grade which requires platelet transfusions,-Grade 4 anaemia unexplained by underlying disease,-Anaemia of any Grade which requires blood transfusions. Non-haematological toxicities: - Aspartate transaminase (AST) or Alanin-Aminotransferase (ALT) >3 times Upper Level of Normal (ULN) and concurrent total bilirubin >2 times ULN without initial findings of cholestasis,-≥ Grade 4 AST or ALT of any duration.
Measured: First treatment cycle, the first 21 days following the start of trial medication.
Secondary outcomes (10)
Maximum Measured Concentration of BI 836880 in Part 1 and Part 2 in Plasma (Cmax) at Cycle 1
Maximum measured concentration of BI 836880 at Cycle 1 in Part 1 (monotherapy) and Part 2 (combination therapy) in plasma (Cmax) is reported.
Measured: Part 1(P1): Within 5 minutes(min) before, at 1 hour(h), 1.5h, 2.5h, 4.5h, 7.5h, 24h, 48h, 168h, 336h after Cycle 1 dose. Part 2(P2): Within 5 min before and at 1h, 2h15min, 6h, 24h, 168h, 336h after Cycle 1 dose. P1,P2: Within 5min before Cycle 2 dose.
Area Under the Concentration-time Curve of BI 836880 in Part 1 and Part 2 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) at Cycle 1
Area under the concentration-time curve of BI 836880 in Part 1 (monotherapy) and in Part 2 (combination therapy) in plasma over the time interval from 0 to 504 hours (AUC0-504h) is reported.
Measured: Part 1(P1): Within 5 minutes(min) before and at 1 hour(h), 1.5h, 2.5h, 4.5h, 7.5h, 24h, 48h, 168h, 336h after Cycle 1 dose. Part 2(P2): Within 5min before and at 1h, 2h15min, 6h, 24h, 168h, 336h after Cycle 1 dose. P1,P2: Within 5min before Cycle 2 dose.
Maximum Measured Concentration of BI 836880 in Part 1 in Plasma (Cmax) at Cycle 2
Maximum measured concentration of BI 836880 at Cycle 2 in Part 1 (monotherapy) in plasma (Cmax) is reported.
Measured: Within 5 minutes (min) before and at 1 hour (h), 1.5h, 2.5h, 4.5h, 7.5h, 24h, 48h, 168h, 336h after dose in Cycle 2. Also, Within 5 min before Cycle 3 dose.
Area Under the Concentration-time Curve of BI 836880 in Part 1 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) at Cycle 2
Area under the concentration-time curve of BI 836880 in Part 1 (monotherapy) at Cycle 2 in plasma over the time interval from 0 to 504 hours (AUC0-504h) is reported.
Measured: Within 5 minutes (min) before and at 1 hour (h), 1.5h, 2.5h, 4.5h, 7.5h, 24h, 48h, 168h, 336h after dose in Cycle 2. Also, Within 5 min before Cycle 3 dose.
Maximum Measured Concentration of BI 836880 in Part 1 and Part 2 in Plasma (Cmax) at Cycle 4
Maximum measured concentration of BI 836880 at Cycle 4 in Part 1 (monotherapy) and Part 2 (combination therapy) in plasma (Cmax) is reported.
Measured: Part 1(P1): Within 5 minutes (min) before and at 1 hour (h), 1.5h, 2.5h, 4.5h, 7.5h, 24h, 168h, 336h after Cycle 4 dose. Part 2(P2): Within 5min before and at 1 h, 2h15min, 6h, 24h, 168h, 336h after Cycle 4 dose. P1,P2: Within 5min before Cycle 5 dose.
Area Under the Concentration-time Curve of BI 836880 in Part1 and Part 2 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) at Cycle 4
Area under the concentration-time curve of BI 836880 in Part 1 (monotherapy) and in Part 2 (combination therapy) at Cycle 4 in plasma over the time interval from 0 to 504 hours (AUC0-504h) is reported.
Measured: Part 1(P1): Within 5 minutes (min) before and at 1 hour (h), 1.5h, 2.5h, 4.5h, 7.5h, 24h, 168h, 336h after Cycle 4 dose. Part 2(P2): Within 5min before and at 1 h, 2h15min, 6h, 24h, 168h, 336h after Cycle 4 dose. P1,P2: Within 5min before Cycle 5 dose.
Maximum Measured Concentration of Ezabenlimab (BI 754091) in Part 2 in Plasma (Cmax) at Cycle 1
Maximum measured concentration of Ezabenlimab (BI 754091) at Cycle 1 in Part 2 (combination therapy) in plasma (Cmax) is reported.
Measured: Within 5 min before and at 1h, 2h15min, 6h, 24h, 168h, 336h after Cycle 1 dose. Also, Within 5 min before Cycle 2 dose.
Area Under the Concentration-time Curve of Ezabenlimab (BI 754091) in Part 2 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) at Cycle 1
Area under the concentration-time curve of Ezabenlimab (BI 754091) in Part 2 (combination therapy) in plasma over the time interval from 0 to 504 hours (AUC0-504h) is reported.
Measured: Within 5 min before and at 1h, 2h15min, 6h, 24h, 168h, 336h after Cycle 1 dose. Also, Within 5 min before Cycle 2 dose.
Maximum Measured Concentration of Ezabenlimab (BI 754091) in Part 2 in Plasma (Cmax) at Cycle 4
Maximum measured concentration of Ezabenlimab (BI 754091) at Cycle 4 in Part 2 (combination therapy) in plasma (Cmax) is reported.
Measured: Within 5 min before and at 1 h, 2h15min, 6h, 24h, 168h, 336h after dosing in Cycle 4. Also, Within 5 min before Cycle 5 dose.
Area Under the Concentration-time Curve of Ezabenlimab (BI 754091) in Part 2 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) at Cycle 4
Area under the concentration-time curve of Ezabenlimab (BI 754091) in Part 2 (combination therapy) in plasma over the time interval from 0 to 504 hours (AUC0-504h) is reported.
Measured: Within 5 min before and at 1 h, 2h15min, 6h, 24h, 168h, 336h after dosing in Cycle 4. Also, Within 5 min before Cycle 5 dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2019
- Study start12 Jun 2019
- Primary completion27 Oct 2020
- Study completion28 Mar 2022
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
- Sequential
- Masking
- None (open label)
- Enrolment
- 21 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
- NCT03972150
- Sponsor's protocol ID
- 1336-0012
- Status last verified
- Sep 2025
- First submitted
- 31 May 2019
- Last updated
- 6 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- 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
Yamamoto N, Koyama T, Shimizu T, Todaka A, Kawakami T, Erzen D, Sarashina A, Li B, Hou J, Yamazaki K. Phase I study of the VEGF/Ang-2 inhibitor BI 836880 alone or combined with the anti-programmed cell death protein-1 antibody ezabenlimab in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2023 Jun;91(6):469-480. doi: 10.1007/s00280-023-04527-6. Epub 2023 May 4.
PubMed 37140602
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Phase I Study of BI 836880 Monotherapy and Combination Therapy of BI 836880 and BI 754091 in Japanese Patients With Advanced Solid Tumours
- ClinicalTrials.gov ID
- NCT03972150
- Acronym / sponsor ID
- 1336-0012
- Conditions
- Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 12 Jun 2019 (actual)
- Primary completion
- 27 Oct 2020 (actual)
- Study completion
- 28 Mar 2022 (actual)
- First posted
- 3 Jun 2019 (actual)
- Results
- Posted 6 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this trial is:
Part I
- To determine Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BI 836880 monotherapy Part II
- To determine MTD and/or RP2D of the combination therapy of BI 836880 and BI 754091
The secondary objectives are:
Part I
- To document the safety and tolerability, and characterise pharmacokinetics (PK) of BI 836880 as monotherapy Part II
- To document the safety and tolerability, and characterise PK of the combination therapy of BI 836880 and BI 754091
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part 1: 360 mg BI 836880 | Experimental | Drug: BI 836880Patients with advanced solid tumors were administered intravenously (i.v.) 360 milligram (mg) of BI 836880 solution for infusion on Day 1 of each 3-week cycle until progressive disease, unacceptable toxicity, or other withdrawal criteria were met (Part 1). |
| Part 1: 720 mg BI 836880 | Experimental | Drug: BI 836880Patients with advanced solid tumors were administered intravenously (i. v.) 720 milligram (mg) of BI 836880 solution for infusion on Day 1 of each 3-week cycle until progressive disease, unacceptable toxicity, or other withdrawal criteria were met (Part 1). |
| Part 2: 120 mg of BI 836880/ 240 mg Ezabenlimab | Experimental | Drug: BI 836880, Drug: BI 754091Patients with advanced solid tumors were administered intravenously (i. v.) 120 milligram (mg) of BI 836880 solution for infusion and 240 mg Ezabenlimab (BI 754091) solution for infusion on Day 1 of each 3-week cycle until progressive disease, unacceptable toxicity, or other withdrawal criteria were met (Part 2). Part 2 commenced after completion of Part 1. |
| Part 2: 360 mg BI 836880/ 240 mg Ezabenlimab | Experimental | Drug: BI 836880, Drug: BI 754091Patients with advanced solid tumors were administered intravenously (i. v.) 360 milligram (mg) of BI 836880 solution for infusion and 240 mg Ezabenlimab (BI 754091) solution for infusion on Day 1 of each 3-week cycle until progressive disease, unacceptable toxicity, or other withdrawal criteria were met (Part 2). Part 2 commenced after completion of Part 1. |
| Part 2: 720 mg BI 836880 / 240 mg Ezabenlimab | Experimental | Drug: BI 836880, Drug: BI 754091Patients with advanced solid tumors were administered intravenously (i. v.) 720 milligram (mg) of BI 836880 solution for infusion and 240 mg Ezabenlimab (BI 754091) solution for infusion on Day 1 of each 3-week cycle until progressive disease, unacceptable toxicity, or other withdrawal criteria were met (Part 2). Part 2 commenced after completion of Part 1. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Of legal age (according to local legislation) at screening. No upper limit.
- Signed and dated written informed consent in accordance with International Council on Harmonisation (ICH) Good Clinical Practice (GCP) and local legislation prior to admission to the trial.
- 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 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 study treatment. A list of contraception methods meeting these criteria is provided in the patient information. The requirement of contraception does not apply to women of no childbearing potential and men not able to father a child, but they must have an evidence of such at screening.
- Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours (any type). Measurable lesion not mandatory for participation in this trial.
- Patients with no therapy of proven efficacy, or who are not amenable to standard therapies.
Key exclusion criteria (26 listed)
- 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 history of human immunodeficiency virus (HIV) infection. Test results obtained in routine diagnostics are acceptable if done within 14 days before the informed consent date.
- Any of the following laboratory evidence of hepatitis virus infection.
- History of severe known 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.
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 |
|---|---|---|
| BI 836880Solution for infusion | Drug | Part 1: 360 mg BI 836880, Part 1: 720 mg BI 836880, Part 2: 120 mg of BI 836880/ 240 mg Ezabenlimab, Part 2: 360 mg BI 836880/ 240 mg Ezabenlimab, Part 2: 720 mg BI 836880 / 240 mg Ezabenlimab |
| BI 754091Solution for infusion | Drug | Part 2: 120 mg of BI 836880/ 240 mg Ezabenlimab, Part 2: 360 mg BI 836880/ 240 mg Ezabenlimab, Part 2: 720 mg BI 836880 / 240 mg Ezabenlimab |
Primary outcome
Maximum Tolerated Dose (MTD) of BI 836880 Monotherapy and Combination Therapy of BI 836880 and BI754091
Time frame: First treatment cycle, the first 21 days following the start of trial medication.
Maximum tolerated dose (MTD) of BI 836880 monotherapy (Part 1) and combination therapy of BI 836880 and BI75409 (Part 2). The MTD was defined as the highest dose with less than 25% risk of the true dose-limiting toxicity (DLT) rate being equal or above 0.33 (EWOC criterion) during the MTD evaluation period. The analysis of the MTD was based on a Bayesian logistic regression model (BLRM) guided by the escalation with overdose control principle. The estimated probability of a DLT at each dose level from the model was summarized using the following intervals: Underdosing: [0.00, 0.16) Targeted toxicity: [0.16, 0.33) Over toxicity: [0.33, 1.00]
Number of Participants With Dose-limiting Toxicity (DLT) During the First Treatment Cycle
Time frame: First treatment cycle, the first 21 days following the start of trial medication.
Number of participants with DLT occurring during the first treatment cycle. DLT was defined as any of the following adverse events related to the treatment: Haematologic toxicities: -Any Grade 5 toxicity,-Neutropenia Grade 4 lasting for >7 days,-Grade ≥3 documented infection with neutropenia,-Febrile neutropenia (absolute neutrophil count <1.0 X 109 cells/L and fever ≥38.5C or a sustained temperature of ≥38.0 Centigrade (C) for more than 1 hour),-Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding,-Thrombocytopenia of any Grade which requires platelet transfusions,-Grade 4 anaemia unexplained by underlying disease,-Anaemia of any Grade which requires blood transfusions. Non-haematological toxicities: - Aspartate transaminase (AST) or Alanin-Aminotransferase (ALT) >3 times Upper Level of Normal (ULN) and concurrent total bilirubin >2 times ULN without initial findings of cholestasis,-≥ Grade 4 AST or ALT of any duration.
10 secondary outcomes
Maximum Measured Concentration of BI 836880 in Part 1 and Part 2 in Plasma (Cmax) at Cycle 1
Time frame: Part 1(P1): Within 5 minutes(min) before, at 1 hour(h), 1.5h, 2.5h, 4.5h, 7.5h, 24h, 48h, 168h, 336h after Cycle 1 dose. Part 2(P2): Within 5 min before and at 1h, 2h15min, 6h, 24h, 168h, 336h after Cycle 1 dose. P1,P2: Within 5min before Cycle 2 dose.
Area Under the Concentration-time Curve of BI 836880 in Part 1 and Part 2 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) at Cycle 1
Time frame: Part 1(P1): Within 5 minutes(min) before and at 1 hour(h), 1.5h, 2.5h, 4.5h, 7.5h, 24h, 48h, 168h, 336h after Cycle 1 dose. Part 2(P2): Within 5min before and at 1h, 2h15min, 6h, 24h, 168h, 336h after Cycle 1 dose. P1,P2: Within 5min before Cycle 2 dose.
Maximum Measured Concentration of BI 836880 in Part 1 in Plasma (Cmax) at Cycle 2
Time frame: Within 5 minutes (min) before and at 1 hour (h), 1.5h, 2.5h, 4.5h, 7.5h, 24h, 48h, 168h, 336h after dose in Cycle 2. Also, Within 5 min before Cycle 3 dose.
Area Under the Concentration-time Curve of BI 836880 in Part 1 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) at Cycle 2
Time frame: Within 5 minutes (min) before and at 1 hour (h), 1.5h, 2.5h, 4.5h, 7.5h, 24h, 48h, 168h, 336h after dose in Cycle 2. Also, Within 5 min before Cycle 3 dose.
Maximum Measured Concentration of BI 836880 in Part 1 and Part 2 in Plasma (Cmax) at Cycle 4
Time frame: Part 1(P1): Within 5 minutes (min) before and at 1 hour (h), 1.5h, 2.5h, 4.5h, 7.5h, 24h, 168h, 336h after Cycle 4 dose. Part 2(P2): Within 5min before and at 1 h, 2h15min, 6h, 24h, 168h, 336h after Cycle 4 dose. P1,P2: Within 5min before Cycle 5 dose.
Area Under the Concentration-time Curve of BI 836880 in Part1 and Part 2 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) at Cycle 4
Time frame: Part 1(P1): Within 5 minutes (min) before and at 1 hour (h), 1.5h, 2.5h, 4.5h, 7.5h, 24h, 168h, 336h after Cycle 4 dose. Part 2(P2): Within 5min before and at 1 h, 2h15min, 6h, 24h, 168h, 336h after Cycle 4 dose. P1,P2: Within 5min before Cycle 5 dose.
Maximum Measured Concentration of Ezabenlimab (BI 754091) in Part 2 in Plasma (Cmax) at Cycle 1
Time frame: Within 5 min before and at 1h, 2h15min, 6h, 24h, 168h, 336h after Cycle 1 dose. Also, Within 5 min before Cycle 2 dose.
Area Under the Concentration-time Curve of Ezabenlimab (BI 754091) in Part 2 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) at Cycle 1
Time frame: Within 5 min before and at 1h, 2h15min, 6h, 24h, 168h, 336h after Cycle 1 dose. Also, Within 5 min before Cycle 2 dose.
Maximum Measured Concentration of Ezabenlimab (BI 754091) in Part 2 in Plasma (Cmax) at Cycle 4
Time frame: Within 5 min before and at 1 h, 2h15min, 6h, 24h, 168h, 336h after dosing in Cycle 4. Also, Within 5 min before Cycle 5 dose.
Area Under the Concentration-time Curve of Ezabenlimab (BI 754091) in Part 2 in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504h) at Cycle 4
Time frame: Within 5 min before and at 1 h, 2h15min, 6h, 24h, 168h, 336h after dosing in Cycle 4. Also, Within 5 min before Cycle 5 dose.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37140602Yamamoto N, Koyama T, Shimizu T, Todaka A, Kawakami T, Erzen D, Sarashina A, Li B, Hou J, Yamazaki K. Phase I study of the VEGF/Ang-2 inhibitor BI 836880 alone or combined with the anti-programmed cell death protein-1 antibody ezabenlimab in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2023 Jun;91(6):469-480. doi: 10.1007/s00280-023-04527-6. Epub 2023 May 4.
- 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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BI 836880 and BI 754091 in people with Neoplasms, run by Boehringer Ingelheim at 2 sites in Japan.
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 9 inclusion and 26 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 6 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Japan. 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 6 Oct 2025). 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?
Maximum Tolerated Dose (MTD) of BI 836880 Monotherapy and Combination Therapy of BI 836880 and BI754091 (time frame: First treatment cycle, the first 21 days following the start of trial medication.). The study lists 2 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 NCT03972150, 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 6 Oct 2025.