Clinical Trials List
Protocol Number1381-0004
NCT Number(ClinicalTrials.gov Identfier)NCT03433898
2018-03-05 - 2021-11-21
Phase I
Terminated6
ICD-10C80.1
Malignant (primary) neoplasm, unspecified
An Open Label, Phase I Study of BI 754091 Monotherapy and Combination Therapy of BI 754091 and BI 754111 in Asian Patients With Advanced Solid Tumours
-
Trial Applicant
Boehringer Ingelheim
-
Sponsor
Boehringer Ingelheim
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chueh-Chuan Yen Division of Hematology & Oncology
- 陳盛裕 Division of Hematology & Oncology
- Ming-Huang Chen Division of Hematology & Oncology
- Yi-Ping Hung Division of Hematology & Oncology
- Chung-Pin Li Division of Hematology & Oncology
- Rheun-Chuan Lee Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Yan-Shen Shan Division of General Internal Medicine
- Chia-Jui Yen Division of General Internal Medicine
- Shang-Yin Wu Division of General Internal Medicine
- Li-Tzong Chen Division of General Internal Medicine
- Kwang-Yu Chang Division of General Internal Medicine
- Shang-Hung Chen Division of General Internal Medicine
- Hui-Jen Tsai Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Linkou Chang Gung Medical Foundation
Taiwan National PI
陳仁熙
Co-Principal Investigator
- Tsai-Sheng Yang Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
- Hung-Chih Hsu Division of Hematology & Oncology
- Wen-Chi Chou Division of Hematology & Oncology
- Chia-Hsun Hsieh Division of Hematology & Oncology
- Cheng-Lung Hsu Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- Kun-Huei Yeh Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- JHE-CYUAN GUO Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- YU-YUN SHAO Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Advanced solid tumor
Objectives
The main objectives of the BI 754091 monotherapy dose-finding part (Part I) of the trial are to investigate the following items in advanced solid tumours:
Safety, tolerability, and pharmacokinetics (PK) of BI 754091 as monotherapy.
Maximum tolerated dose (MTD) and/or recommended dose (RD) of BI 754091 monotherapy.
The main objectives of the Combination dose-finding part (Part II) of the trial are to investigate the following items in advanced solid tumours:
Safety, tolerability, and PK of the combination treatment of BI 754091 and BI 754111.
MTD and/or RD of the combination treatment of BI 754091 and BI 754111.
The main objectives of the expansion part (Part III) of the trial are:
To further investigate the safety, tolerability, and PK of the RD of BI 754091 and BI 754111 combination in patients with gastric/esophagogastric junction cancer, esophageal cancer, hepatocellular cancer or non-small cell lung cancer (NSCLC)
To explore the efficacy of the RD of the combination of BI 754091 and BI 754111 in patients with gastric/esophagogastric junction cancer, esophageal cancer, hepatocellular cancer or NSCLC
Test Drug
BI 754091/BI 754111
Active Ingredient
BI 7540091
BI 754111
BI 754111
Dosage Form
solution for infusion
solution for infusion
solution for infusion
Dosage
300mg/15ml[20mg/ml]
300mg/15ml[20mg/ml]
300mg/15ml[20mg/ml]
Endpoints
Primary Outcome Measures :
Part I: Maximum tolerated dose (MTD) of BI 754091 [ Time Frame: Up to 9 months ]
Part I: Number of patients experiencing dose limiting toxicities (DLTs) during the MTD evaluation period (first cycle of treatment) [ Time Frame: Up to 3 weeks ]
Part II: MTD of the BI 754091 plus BI 754111 combination [ Time Frame: Up to 9 months ]
Part II: Number of patients experiencing DLTs during the MTD evaluation period (first cycle of treatment) [ Time Frame: Up to 3 weeks ]
Part III: Objective response (OR) - confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumours (RECIST) Version 1.1 as assessed by the Investigator [ Time Frame: Up to 12 months ]
Part I: Maximum tolerated dose (MTD) of BI 754091 [ Time Frame: Up to 9 months ]
Part I: Number of patients experiencing dose limiting toxicities (DLTs) during the MTD evaluation period (first cycle of treatment) [ Time Frame: Up to 3 weeks ]
Part II: MTD of the BI 754091 plus BI 754111 combination [ Time Frame: Up to 9 months ]
Part II: Number of patients experiencing DLTs during the MTD evaluation period (first cycle of treatment) [ Time Frame: Up to 3 weeks ]
Part III: Objective response (OR) - confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumours (RECIST) Version 1.1 as assessed by the Investigator [ Time Frame: Up to 12 months ]
Inclution Criteria
Inclusion criteria
1. Of full age (according to local legislation) at the time of signing of the informed consent
form (ICF)
2. Women of childbearing potential (WOCBP)
1 with negative serum pregnancy test at
screening and men able to father a child, who agree 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. 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 but they must have an evidence of such at
screening
3. Signed and dated written informed consent in accordance with ICH-GCP and local
legislation prior to admission to the trial
4. Patients with measurable lesions according to RECIST v1.1
5. Conditions specific to respective part of the trial:
o Part I (BI 754091 dose-finding part):
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.
Previous treatment with an anti-PD-1 mAb is allowed as long as the last
administration of the anti-PD-1 mAb on the previous treatment is a
minimum of 28 days prior to the first BI 754091 treatment.
o Part II (Combination dose-finding part):
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.
Previous treatment with an anti-PD-1 mAb is allowed as long as the last
administration of the anti-PD-1 mAb on the previous treatment is a
minimum of 28 days prior to the first BI 754091 treatment.
o Part III (Expansion part):
Cohort A: Patients with gastric/esophagogastric junction cancer, with no
prior treatment with anti-PD-1/PD-L1 antibody, and who received at least
one line of systemic medical treatment excluding adjuvant therapy
Cohort B: Patients with esophageal cancer with no prior treatment with
anti-PD-1/PD-L1 antibody, and who received at least one line of systemic
medical treatment excluding adjuvant therapy
Cohort C: Patients with hepatocellular cancer with no prior treatment with
anti-PD-1/PD-L1 antibody, who received at least one line of systemic
medical treatment excluding adjuvant therapy, and whose Child-Pugh
score is 7 or less
Cohort D: Patients with gastric/esophagogastric junction cancer,
esophageal cancer, or hepatocellular cancer with a prior treatment with
anti-PD-1/PD-L1 antibody
All cohorts: Patients with advanced and/or metastatic disease, with at least
1 tumour lesion amenable to biopsy, and must be medically fit for biopsy
at screening as determined by investigator 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.
6. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance status (PS): 0 to 1
at screening
1. Of full age (according to local legislation) at the time of signing of the informed consent
form (ICF)
2. Women of childbearing potential (WOCBP)
1 with negative serum pregnancy test at
screening and men able to father a child, who agree 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. 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 but they must have an evidence of such at
screening
3. Signed and dated written informed consent in accordance with ICH-GCP and local
legislation prior to admission to the trial
4. Patients with measurable lesions according to RECIST v1.1
5. Conditions specific to respective part of the trial:
o Part I (BI 754091 dose-finding part):
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.
Previous treatment with an anti-PD-1 mAb is allowed as long as the last
administration of the anti-PD-1 mAb on the previous treatment is a
minimum of 28 days prior to the first BI 754091 treatment.
o Part II (Combination dose-finding part):
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.
Previous treatment with an anti-PD-1 mAb is allowed as long as the last
administration of the anti-PD-1 mAb on the previous treatment is a
minimum of 28 days prior to the first BI 754091 treatment.
o Part III (Expansion part):
Cohort A: Patients with gastric/esophagogastric junction cancer, with no
prior treatment with anti-PD-1/PD-L1 antibody, and who received at least
one line of systemic medical treatment excluding adjuvant therapy
Cohort B: Patients with esophageal cancer with no prior treatment with
anti-PD-1/PD-L1 antibody, and who received at least one line of systemic
medical treatment excluding adjuvant therapy
Cohort C: Patients with hepatocellular cancer with no prior treatment with
anti-PD-1/PD-L1 antibody, who received at least one line of systemic
medical treatment excluding adjuvant therapy, and whose Child-Pugh
score is 7 or less
Cohort D: Patients with gastric/esophagogastric junction cancer,
esophageal cancer, or hepatocellular cancer with a prior treatment with
anti-PD-1/PD-L1 antibody
All cohorts: Patients with advanced and/or metastatic disease, with at least
1 tumour lesion amenable to biopsy, and must be medically fit for biopsy
at screening as determined by investigator 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.
6. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance status (PS): 0 to 1
at screening
Exclusion Criteria
Exclusion criteria
1. Major surgery (major according to the investigator’s assessment) performed within 12
weeks prior to study entry or planned within 12 months after screening, e.g. hip
replacement
2. 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
3. Previous treatment with study medications in this trial
4. Any investigational or anti-tumour treatment within 4 weeks or 5 half-life periods
(whichever is shorter) prior to the initiation of trial treatment
5. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria
for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the
exception of alopecia and Grade 2 neuropathy due to chemotherapy
6. (Part II and III only) Prior treatment with anti-LAG-3 agents
7. Patients with lung cancer that have epidermal growth factor receptor (EGFR) mutations
or anaplastic lymphoma kinase (ALK) rearrangements, unless disease has progressed
following available EGFR or ALK targeted therapy
8. Presence of other active invasive cancers other than the one treated in this trial, with the
exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma
in situ of the cervix, or other local tumours considered cured by local treatment
9. 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
10. Inadequate organ function or bone marrow reserve as demonstrated by the following
laboratory values:
o Absolute neutrophil count <1.5 x 109
/L (<1500/mm3
)
o Platelet count <100 x 109
/L (<100,000/mm3
)
o Haemoglobin <9.0 g/dL
o Alanine aminotransferase (ALT) >2.5 times the upper limit of normal (ULN) if no
demonstrable liver metastases or >5 times ULN in the presence of liver metastases
o Aspartate aminotransferase (AST) >2.5 times ULN if no demonstrable liver
metastases or >5 times ULN in the presence of liver metastases
o Total bilirubin >1.5 times ULN, except for patients with Gilbert's syndrome who
are excluded if total bilirubin >3.0 times ULN or direct bilirubin >1.5 times ULN
o Serum creatinine (measured by enzymatic assay, Isotope dilution mass
spectroscopy [IDMS] standardized Jaffe assay, or non-IDMS Jaffe assay) >1.5 times ULN or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2
(Chronic Kidney Disease Epidemiology [CKD-EPI] Collaboration equation);
confirmation of eGFR is only required when creatinine is >1.5 X ULN
o International normalized ratio (INR) (only tested if clinically indicated) >1.5 times
ULN (if treated with anticoagulants, prolonged INR is acceptable)
11. Any of the following cardiac criteria:
o Mean resting corrected QT interval (QTc) >470 msec
o Any clinically important abnormalities in rhythm, conduction, or morphology of
resting ECGs, e.g., complete left bundle branch block, third degree heart block
o 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
o Ejection fraction <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 [ECHO], multi-gated
acquisition scan [MUGA]). 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.
12. History (including current) of interstitial lung disease or pneumonitis within the last 5
years
13. History of severe hypersensitivity reactions to other mAbs
14. History of severe hypersensitivity reactions to the ingredients of study drug
15. Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within
4 weeks prior to the first dose of study treatment
16. Active autoimmune disease or a documented history of autoimmune disease, except
vitiligo or resolved childhood asthma/atopy
17. Active infection requiring systemic treatment (antibacterial, antiviral, or antifungal
therapy) at start of treatment in this trial
18. 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
19. Any of the following laboratory evidence of hepatitis virus infection. Test results
obtained in routine diagnostics are acceptable if done within 14 days before the informed
consent date
o Positive results of hepatitis B surface (HBs) antigen
o Presence of HBc antibody together with HBV-DNA
o Presence of hepatitis C RNA
However, for patients with hepatocellular cancer in Part III Cohorts C and D, patients
with HBV and/or HCV infection are allowed. Hepatocellular cancer patients in Part III
Cohorts C and D with HBV infection must be receiving effective antiviral therapy (viral
load <100 IU/mL)
20. Chronic alcohol or drug abuse or any condition that, in the investigator’s opinion, makes
him/her an unreliable trial patient, unlikely to complete the trial, or unable to comply with the protocol procedures. However, in Part III Cohort C, patients with past chronic alcohol
abuse are allowed
21. Women who are pregnant, nursing, or who plan to become pregnant during the trial.
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.
1. Major surgery (major according to the investigator’s assessment) performed within 12
weeks prior to study entry or planned within 12 months after screening, e.g. hip
replacement
2. 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
3. Previous treatment with study medications in this trial
4. Any investigational or anti-tumour treatment within 4 weeks or 5 half-life periods
(whichever is shorter) prior to the initiation of trial treatment
5. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria
for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the
exception of alopecia and Grade 2 neuropathy due to chemotherapy
6. (Part II and III only) Prior treatment with anti-LAG-3 agents
7. Patients with lung cancer that have epidermal growth factor receptor (EGFR) mutations
or anaplastic lymphoma kinase (ALK) rearrangements, unless disease has progressed
following available EGFR or ALK targeted therapy
8. Presence of other active invasive cancers other than the one treated in this trial, with the
exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma
in situ of the cervix, or other local tumours considered cured by local treatment
9. 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
10. Inadequate organ function or bone marrow reserve as demonstrated by the following
laboratory values:
o Absolute neutrophil count <1.5 x 109
/L (<1500/mm3
)
o Platelet count <100 x 109
/L (<100,000/mm3
)
o Haemoglobin <9.0 g/dL
o Alanine aminotransferase (ALT) >2.5 times the upper limit of normal (ULN) if no
demonstrable liver metastases or >5 times ULN in the presence of liver metastases
o Aspartate aminotransferase (AST) >2.5 times ULN if no demonstrable liver
metastases or >5 times ULN in the presence of liver metastases
o Total bilirubin >1.5 times ULN, except for patients with Gilbert's syndrome who
are excluded if total bilirubin >3.0 times ULN or direct bilirubin >1.5 times ULN
o Serum creatinine (measured by enzymatic assay, Isotope dilution mass
spectroscopy [IDMS] standardized Jaffe assay, or non-IDMS Jaffe assay) >1.5 times ULN or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2
(Chronic Kidney Disease Epidemiology [CKD-EPI] Collaboration equation);
confirmation of eGFR is only required when creatinine is >1.5 X ULN
o International normalized ratio (INR) (only tested if clinically indicated) >1.5 times
ULN (if treated with anticoagulants, prolonged INR is acceptable)
11. Any of the following cardiac criteria:
o Mean resting corrected QT interval (QTc) >470 msec
o Any clinically important abnormalities in rhythm, conduction, or morphology of
resting ECGs, e.g., complete left bundle branch block, third degree heart block
o 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
o Ejection fraction <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 [ECHO], multi-gated
acquisition scan [MUGA]). 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.
12. History (including current) of interstitial lung disease or pneumonitis within the last 5
years
13. History of severe hypersensitivity reactions to other mAbs
14. History of severe hypersensitivity reactions to the ingredients of study drug
15. Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within
4 weeks prior to the first dose of study treatment
16. Active autoimmune disease or a documented history of autoimmune disease, except
vitiligo or resolved childhood asthma/atopy
17. Active infection requiring systemic treatment (antibacterial, antiviral, or antifungal
therapy) at start of treatment in this trial
18. 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
19. Any of the following laboratory evidence of hepatitis virus infection. Test results
obtained in routine diagnostics are acceptable if done within 14 days before the informed
consent date
o Positive results of hepatitis B surface (HBs) antigen
o Presence of HBc antibody together with HBV-DNA
o Presence of hepatitis C RNA
However, for patients with hepatocellular cancer in Part III Cohorts C and D, patients
with HBV and/or HCV infection are allowed. Hepatocellular cancer patients in Part III
Cohorts C and D with HBV infection must be receiving effective antiviral therapy (viral
load <100 IU/mL)
20. Chronic alcohol or drug abuse or any condition that, in the investigator’s opinion, makes
him/her an unreliable trial patient, unlikely to complete the trial, or unable to comply with the protocol procedures. However, in Part III Cohort C, patients with past chronic alcohol
abuse are allowed
21. Women who are pregnant, nursing, or who plan to become pregnant during the trial.
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.
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
164 participants
