This Study Aims to Find a Safe and Effective Dose of BI 754091. The Study Also Aims to Find Safe and Effective Doses of BI 754091 and BI 754111 in Combination. This Study is Done in Asian Patients With Different Types of Cancer

NCT03433898 | Completed Early Phase 1 Results FDA Drug

• 1 other identifier: 1381-0004
• Study Type: interventional
• Target: 146
• Locations: 3 countries
• Sites: 13

Brief Summary

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

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (5)

• Part I: Maximum Tolerated Dose (MTD) of Ezabenlimab

  MTD is defined as the highest dose for a given schedule expected to cause \<25% risk of the true dose limiting toxicity (DLT) rate being ≥33% during the MTD evaluation period. Haematologic DLTs: any Grade 5 toxicity; neutropenia ≥Grade 4 for \>5 days; any duration Febrile neutropenia; grade 4 thrombocytopenia or Grade 3 with bleeding or requiring platelet transfusions (any Grade); unexplained Grade 4 anaemia or requiring blood transfusions (any Grade). Non-haematological DLTs: aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \>3x Upper limit of normal (ULN) and total bilirubin \>2x ULN without cholestasis signs; any duration ≥Grade 4 AST or ALT; any ≥Grade 3 non-haematologic toxicity with exceptions; any Grade 4 or 5 adverse event; any duration any Grade 2 pneumonitis; any Grade 2 uveitis, eye pain, or blurred vision not improving to Grade 1 within 2 weeks or requiring systemic treatment; any ≥Grade 2 toxicity causing inability to administer trial drug on Cycle 2 Day 1.

  First cycle of treatment: 3 weeks (21 days) following drug administration.

• Part I: Number of Patients Experiencing DLTs During the MTD Evaluation Period (First Cycle of Treatment)

  Number of patients experiencing DLTs during the MTD evaluation period (first cycle of treatment) is reported.

  First cycle of treatment: 3 weeks (21 days) following drug administration.

• Part II: MTD of the Ezabenlimab Plus BI 754111 Combination Therapy

  MTD is defined as the highest dose for a given schedule expected to cause \<25% risk of the true DLT rate being ≥33% during the MTD evaluation period. Haematologic DLTs: any Grade 5 toxicity; neutropenia ≥Grade 4 for \>5 days; any duration Febrile neutropenia; grade 4 thrombocytopenia or Grade 3 with bleeding or requiring platelet transfusions (any Grade); unexplained Grade 4 anaemia or requiring blood transfusions (any Grade). Non-haematological DLTs: aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \>3x Upper limit of normal (ULN) and total bilirubin \>2x ULN without cholestasis signs; any duration ≥Grade 4 AST or ALT; any ≥Grade 3 non-haematologic toxicity with exceptions; any Grade 4 or 5 adverse event; any duration any Grade 2 pneumonitis; any Grade 2 uveitis, eye pain, or blurred vision not improving to Grade 1 within 2 weeks or requiring systemic treatment; any ≥Grade 2 toxicity causing inability to administer trial drugs on Cycle 2 Day 1.

  First cycle of treatment: 3 weeks (21 days) following drug administration.

• Part II: Number of Patients Experiencing DLTs During the MTD Evaluation Period (First Cycle of Treatment)

  Number of patients experiencing DLTs during the MTD evaluation period (first cycle of treatment) is reported.

  First cycle of treatment: 3 weeks (21 days) following drug administration.

• Part III: Number of Patients With 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

  Number of patients with 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, is reported. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period): up to 49 months.

Secondary Outcomes (10)

• Part III: Duration of Response

  From the date of objective response until first date that death or PD has been documented, up to 1362 days.

• Part III: Number of Patients With Disease Control

  From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period): up to 49 months.

• Part I: Number of Patients With OR: Confirmed CR or PR According to RECIST v1.1 as Assessed by the Investigator

  From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period): 180 days.

• Part II: Number of Patients With OR: Confirmed CR or PR According to RECIST v1.1 as Assessed by the Investigator

  From the date of the first administration of trial treatment until the date of the last administration of trial treatment + 30 days (residual effect period): up to 389 days.

• Part I: Maximum Measured Concentration of Ezabenlimab in Plasma (Cmax) in the First Cycle of Treatment

  5 minutes before drug administration and 1, 1.5, 2, 4, 7, 24, 48, 72, 168, 336 and 504 hours (h) after the start of drug administration in the first cycle of treatment.

Study Arms (8)

Part I - ezabenlimab 240 mg

EXPERIMENTAL

Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.

Drug: Ezabenlimab

Part II - ezabenlimab 240 mg + BI 754111 400 mg

EXPERIMENTAL

Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 400 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.

Drug: Ezabenlimab; Drug: BI 754111

Part II - ezabenlimab 240 mg + BI 754111 600 mg

EXPERIMENTAL

Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.

Drug: Ezabenlimab; Drug: BI 754111

Part II - ezabenlimab 240 mg + BI 754111 800 mg

EXPERIMENTAL

Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 800 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.

Drug: Ezabenlimab; Drug: BI 754111

Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort A

EXPERIMENTAL

Patients with gastric/esophagogastric junction cancer, with no prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, and who had received at least one line of systemic anticancer treatment, excluding adjuvant therapy, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.

Drug: Ezabenlimab; Drug: BI 754111

Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort B

EXPERIMENTAL

Patients with esophageal cancer, with no prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, and who had received at least one line of systemic anticancer treatment, excluding adjuvant therapy, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.

Drug: Ezabenlimab; Drug: BI 754111

Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort C

EXPERIMENTAL

Patients with hepatocellular cancer, with no prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, who received at least one line of systemic anticancer treatment, excluding adjuvant therapy, and whose Child-Pugh score is ≤7, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.

Drug: Ezabenlimab; Drug: BI 754111

Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort D

EXPERIMENTAL

Patients with gastric/esophagogastric junction cancer, esophageal cancer, or hepatocellular cancer, with a prior treatment with anti-Programmed cell death protein-1 (PD-1)/Programmed death ligand-1 (PD-L1) antibody, were administered via intravenous infusion with ezabenlimab 240 milligram (mg) and BI 754111 600 mg on day 1 of each 3-week (21 days) cycle. Administration was continued until progressive disease, unacceptable toxicity, other withdrawal criteria, or a maximum treatment duration of 1 year. If the patient was benefiting clinically at 1 year, he/she could continue after a case-by-case review with the sponsor.

Drug: Ezabenlimab; Drug: BI 754111

Interventions

Ezabenlimab DRUG

Solution for infusion

Also known as: BI 754091

Part I - ezabenlimab 240 mg; Part II - ezabenlimab 240 mg + BI 754111 400 mg; Part II - ezabenlimab 240 mg + BI 754111 600 mg; Part II - ezabenlimab 240 mg + BI 754111 800 mg; Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort A; Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort B; Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort C; Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort D

BI 754111 DRUG

Solution for infusion

Part II - ezabenlimab 240 mg + BI 754111 400 mg; Part II - ezabenlimab 240 mg + BI 754111 600 mg; Part II - ezabenlimab 240 mg + BI 754111 800 mg; Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort A; Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort B; Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort C; Part III - ezabenlimab 240 mg + BI 754111 600 mg, cohort D

Eligibility Criteria

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

You may qualify if:

• Of full age (according to local legislation) at the time of signing of the informed consent form (ICF)
• 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
• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
• Patients with measurable lesions according to RECIST v1.1
• Conditions specific to respective part of the trial:
• 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.
• 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.
• 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

You may not qualify if:

• 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
• 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
• Previous treatment with study medications in this trial
• Any investigational or anti-tumour treatment within 4 weeks or 5 half-life periods (whichever is shorter) prior to the initiation of trial treatment
• 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 prior platinum-based therapy
• (Part II and III only) Prior treatment with anti-LAG-3 agents
• 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
• Presence of other active invasive cancers other than the one treated in this Trial within 5 years Prior to screening, with the exception of appropriately treated basal or squamous-cell carcinoma of the skin or in situ carcinoma of the uterine cervix, or other local tumours considered cured by local treatment
• Untreated brain metastasis(es) that may be considered active. Patients with previously treated brain metastases may participate provided they are stable (i.e., without evidence of PD by imaging for at least 4 weeks prior to the first dose of trial treatment, and any neurologic symptoms have returned to baseline), and there is no evidence of new or enlarging brain metastases
• Inadequate organ function or bone marrow reserve as demonstrated by the following laboratory values:
• Absolute neutrophil count \<1.5 x 10\^9/L (\<1500/mm\^3)
• Platelet count \<100 x 10\^9/L (\<100,000/mm\^3)
• Haemoglobin \<9.0 g/dL
• Alanine aminotransferase (ALT) \>2.5 times the upper limit of normal (ULN) if no demonstrable liver lesion(s) (primary or metastases) or \>5 times ULN in the presence of liver lesion(s)
• Aspartate aminotransferase (AST) \>2.5 times ULN if no demonstrable liver lesion(s) or \>5 times ULN in the presence of liver lesion(s)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (13)

National Cancer Center Hospital East

Chiba, Kashiwa, 277-8577, Japan

Location

Kanagawa Cancer Center

Kanagawa, Yokohama, 241-8515, Japan

Location

Saitama Cancer Center

Saitama, Kitaadachi-gun, 362-0806, Japan

Location

Shizuoka Cancer Center

Shizuoka, Sunto-gun, 411-8777, Japan

Location

National Cancer Center Hospital

Tokyo, Chuo-ku, 104-0045, Japan

Location

Japanese Foundation for Cancer Research

Tokyo, Koto-ku, 135-8550, Japan

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

NCKUH

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital(Linkou)

Taoyuan District, 333, Taiwan

Location

Related Publications (1)

• Zettl M, Wurm M, Schaaf O, Mostbock S, Tirapu I, Apfler I, Lorenz IC, Frego L, Kenny C, Thibodeau M, Oquendo Cifuentes E, Reschke M, Moll J, Kraut N, Vogt A, Sedgwick JD, Waizenegger IC. Combination of two novel blocking antibodies, anti-PD-1 antibody ezabenlimab (BI 754091) and anti-LAG-3 antibody BI 754111, leads to increased immune cell responses. Oncoimmunology. 2022 Jun 16;11(1):2080328. doi: 10.1080/2162402X.2022.2080328. eCollection 2022.

  PMID: 35756842 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms

Limitations and Caveats

A Cohort E in part III, composed of first line non-small cell lung cancer patients, was also originally planned. However, the clinical development of the combination therapy of BI 754111 and ezabenlimab was concluded early according to protocol due to lack of efficacy of BI 754111 before Cohort E was initiated, so no patient was enrolled in the cohort.

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: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2018
• First Posted: February 15, 2018
• Study Start: February 23, 2018
• Primary Completion: July 20, 2023
• Study Completion: July 20, 2023
• Last Updated: December 19, 2025
• Results First Posted: December 19, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

JP (6); KR (3); TW (4)