Clinical Trials List
Protocol Number1336-0011
NCT Number(ClinicalTrials.gov Identfier)NCT03468426
Completed
2020-03-01 - 2023-12-31
Phase I
Recruiting2
An Open Label Phase Ib Dose Finding Study of BI 836880 in Combination With BI 754091 to Characterize Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy in Patients With Locally Advanced or Metastatic Non-squamous Non-Small Cell Lung Cancer and in Other Solid Tumors
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Trial Applicant
Boehringer Ingelheim
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Sponsor
Boehringer Ingelheim
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Yu-Min Yeh Division of General Internal Medicine
- Chun-Hui Lee Division of General Internal Medicine
- Shang-Yin Wu Division of General Internal Medicine
- Jui-Hung Tsai Division of General Internal Medicine
- Wen-Pin Su Division of General Internal Medicine
- Po-Lan Su Division of General Internal Medicine
- Chien-Chung Lin Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 廖斌志 Division of Hematology & Oncology
- JIN-YUAN SHIH Division of Hematology & Oncology
- 許嘉林 Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- YEN-TING LIN Division of Hematology & Oncology
- Jih-Hsiang Lee Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of Hematology & Oncology
- 楊景堯 Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- James Chih-Hsin Yang Division of Hematology & Oncology
- Chong-Jen Yu Division of Hematology & Oncology
- 蔡子修 Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- YU-YUN SHAO Division of Hematology & Oncology
- 徐偉勛 Division of Hematology & Oncology
- 廖唯昱 Division of Hematology & Oncology
- 吳尚俊 Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Advanced Solid Tumors
Objectives
This study has 2 parts. The first part is open to adults with advanced non-small cell lung cancer.
The second part is open also to adults with other types of advanced cancer of the lung, brain, skin, and liver. The participants get a combination of two medicines called BI 836880 and BI 754091.
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. BI 754091 is an antibody that may help the immune system fight cancer (immune checkpoint inhibitor).
The purpose of the first part of the study is to find out the highest dose of the BI 836880 that the participants can tolerate in combination with BI 754091. Once the best dose of BI 836880 for the combination with BI 754091 is found, it will be 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 BI 754091 every 3 weeks. The doctors also regularly check the general health of the participants.
Test Drug
BI 754091+BI 836880
Active Ingredient
BI 754091
BI 836880
BI 836880
Dosage Form
Solution for infusion
Solution for infusion
Solution for infusion
Dosage
100mg/10ml
300mg/15ml
300mg/15ml
Endpoints
Primary Outcome Measures :
Part 1: Number of patients with Dose Limiting Toxicities (DLTs) within the first cycle of treatment [ Time Frame: Up to 3 weeks ]
Part 2: Shrinkage estimator of objective response [ Time Frame: Up to 3 years ]
Secondary Outcome Measures :
Part 1: Adverse events (AEs), drug related AEs, drug related AEs leading to dose reduction or discontinuation during treatment period [ Time Frame: Up to 294 days ]
Part 1: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours (AUC 0-504h) after the first infusion cycle [ Time Frame: Up to 504 hours after first infusion cycle ]
Part 1: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours (AUC 0-504h) after the fourth infusion cycle [ Time Frame: Up to 504 hours after fourth infusion cycle ]
Part 1: Maximum measured concentration of the analyte in plasma (Cmax) [ Time Frame: Up to 12 weeks ]
Part 1: Time from dosing to maximum measured concentration of the analyte in plasma (tmax) [ Time Frame: Up to 12 weeks ]
Part 2: Adverse events (AEs), drug related AEs, drug related AEs leading to dose reduction or discontinuation during treatment period [ Time Frame: Up to 294 days ]
Part 2: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours (AUC 0-504h) after the first infusion cycle [ Time Frame: Up to 504 hours after first infusion cycle ]
Part 2: Time from dosing to maximum measured concentration of the analyte in plasma (tmax) [ Time Frame: Up to 12 weeks ]
Part 2: Maximum measured concentration of the analyte in plasma (Cmax) [ Time Frame: Up to 12 weeks ]
Part 2: Disease control (DC) [ Time Frame: Up to 3 years ]
PART 2: Duration of objective response (DoR) [ Time Frame: Up to 3 years ]
Part 2: Progression-free survival (PFS) [ Time Frame: Up to 3 years ]
Part 2: Tumour shrinkage (in millimeters) [ Time Frame: Up to 3 years ]
Part 1: Number of patients with Dose Limiting Toxicities (DLTs) within the first cycle of treatment [ Time Frame: Up to 3 weeks ]
Part 2: Shrinkage estimator of objective response [ Time Frame: Up to 3 years ]
Secondary Outcome Measures :
Part 1: Adverse events (AEs), drug related AEs, drug related AEs leading to dose reduction or discontinuation during treatment period [ Time Frame: Up to 294 days ]
Part 1: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours (AUC 0-504h) after the first infusion cycle [ Time Frame: Up to 504 hours after first infusion cycle ]
Part 1: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours (AUC 0-504h) after the fourth infusion cycle [ Time Frame: Up to 504 hours after fourth infusion cycle ]
Part 1: Maximum measured concentration of the analyte in plasma (Cmax) [ Time Frame: Up to 12 weeks ]
Part 1: Time from dosing to maximum measured concentration of the analyte in plasma (tmax) [ Time Frame: Up to 12 weeks ]
Part 2: Adverse events (AEs), drug related AEs, drug related AEs leading to dose reduction or discontinuation during treatment period [ Time Frame: Up to 294 days ]
Part 2: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours (AUC 0-504h) after the first infusion cycle [ Time Frame: Up to 504 hours after first infusion cycle ]
Part 2: Time from dosing to maximum measured concentration of the analyte in plasma (tmax) [ Time Frame: Up to 12 weeks ]
Part 2: Maximum measured concentration of the analyte in plasma (Cmax) [ Time Frame: Up to 12 weeks ]
Part 2: Disease control (DC) [ Time Frame: Up to 3 years ]
PART 2: Duration of objective response (DoR) [ Time Frame: Up to 3 years ]
Part 2: Progression-free survival (PFS) [ Time Frame: Up to 3 years ]
Part 2: Tumour shrinkage (in millimeters) [ Time Frame: Up to 3 years ]
Inclution Criteria
Part 2:
Of full age (according to local legislation, usually ≥ 18 years) at screening
At least one measurable target lesion outside the brain (excluding the glioblastoma patients where brain lesions are allowed), that can be accurately measured per RECIST version 1.1 or Response Assessment in Neuro-Oncology (RANO)
ECOG performance status ≤ 1 (For glioblastoma cohort Karnofsky status is applicable)
Adequate organ function as all of the following (all screening labs should be performed at local lab within approximately 72 hours prior to treatment initiation)
Availability and willingness to provide a fresh tumor tissue sample obtained after relapse or progression on or after prior therapy. For Part 2, In case a fresh biopsy cannot be obtained (e.g. inaccessible lesions or patient safety concern), an archived specimen obtained up to 6 months prior to cycle 1, visit 1 (C1V1) may be submitted in case no systemic antineoplastic therapy has been administered between the biopsy and C1V1 (except for cohort D). For cohorts E, F and G, a fresh on-treatment biopsy is mandatory at C3D1, if possible from the same lesion as the pre-treatment biopsy.
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
Male or female patients. Women of childbearing potential (WOCBP)2 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, for the entire duration of the trial treatment intake and for 6 months after the end of the trial treatment. 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 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.- Further inclusion criteria apply
Of full age (according to local legislation, usually ≥ 18 years) at screening
At least one measurable target lesion outside the brain (excluding the glioblastoma patients where brain lesions are allowed), that can be accurately measured per RECIST version 1.1 or Response Assessment in Neuro-Oncology (RANO)
ECOG performance status ≤ 1 (For glioblastoma cohort Karnofsky status is applicable)
Adequate organ function as all of the following (all screening labs should be performed at local lab within approximately 72 hours prior to treatment initiation)
Availability and willingness to provide a fresh tumor tissue sample obtained after relapse or progression on or after prior therapy. For Part 2, In case a fresh biopsy cannot be obtained (e.g. inaccessible lesions or patient safety concern), an archived specimen obtained up to 6 months prior to cycle 1, visit 1 (C1V1) may be submitted in case no systemic antineoplastic therapy has been administered between the biopsy and C1V1 (except for cohort D). For cohorts E, F and G, a fresh on-treatment biopsy is mandatory at C3D1, if possible from the same lesion as the pre-treatment biopsy.
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
Male or female patients. Women of childbearing potential (WOCBP)2 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, for the entire duration of the trial treatment intake and for 6 months after the end of the trial treatment. 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 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.- Further inclusion criteria apply
Exclusion Criteria
Part 2:
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 Not more than one CPI based treatment regimen prior to entering study (e.g. anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T lymphocyte associated antigen-4 (anti-CTLA-4) antibody). In case of CPIs combination, they need to be approved by the local regulatory agencies; for e.g., Melanoma cohort (Cohort E).
Known HIV infection
Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (exception for patients in HCC cohorts; Cohorts F& G).
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 except for control of cerebral edema in case of recurrent glioblastoma (cohort D).
Current or prior treatment with any systemic anti-cancer therapy (including radiotherapy) 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.
Patients who require full-dose anticoagulation (according to local guidelines).
No Vitamin K antagonist and other anticoagulation allowed; LMWH allowed only for prevention not for curative treatment.
History of pneumonitis (non-infectious) within the last 5 years
Patients who are under judicial protection and patients who are legally institutionalized.
Patients unable or unwilling to comply with protocol
Previous enrolment in this trial.
Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial.
Women who are pregnant, nursing, or who plan to become pregnant in the trial
UncontrolledSymptomatic pleural effusion, pericardial effusion, or ascites
Prior treatment with any antiangiogenic treatment (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc) except for sorafenib and lenvatinib in 2nd line HCC cohort (Cohort F)
Has received a live vaccine within 30 days prior to the first dose of study drug
Patients with known active second malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast. Patients are not considered to have a currently active malignancy if they have completed anticancer therapy and have been disease free for greater than 2 years prior to screening
Further exclusion criteria apply
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 Not more than one CPI based treatment regimen prior to entering study (e.g. anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T lymphocyte associated antigen-4 (anti-CTLA-4) antibody). In case of CPIs combination, they need to be approved by the local regulatory agencies; for e.g., Melanoma cohort (Cohort E).
Known HIV infection
Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (exception for patients in HCC cohorts; Cohorts F& G).
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 except for control of cerebral edema in case of recurrent glioblastoma (cohort D).
Current or prior treatment with any systemic anti-cancer therapy (including radiotherapy) 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.
Patients who require full-dose anticoagulation (according to local guidelines).
No Vitamin K antagonist and other anticoagulation allowed; LMWH allowed only for prevention not for curative treatment.
History of pneumonitis (non-infectious) within the last 5 years
Patients who are under judicial protection and patients who are legally institutionalized.
Patients unable or unwilling to comply with protocol
Previous enrolment in this trial.
Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial.
Women who are pregnant, nursing, or who plan to become pregnant in the trial
UncontrolledSymptomatic pleural effusion, pericardial effusion, or ascites
Prior treatment with any antiangiogenic treatment (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc) except for sorafenib and lenvatinib in 2nd line HCC cohort (Cohort F)
Has received a live vaccine within 30 days prior to the first dose of study drug
Patients with known active second malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast. Patients are not considered to have a currently active malignancy if they have completed anticancer therapy and have been disease free for greater than 2 years prior to screening
Further exclusion criteria apply
The Estimated Number of Participants
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Taiwan
12 participants
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Global
255 participants
