A Trial to Find and Investigate a Safe Dose of a New Substance (BI 754091) for Patients With Solid Tumours

An Open-label, Phase I Trial to Determine the Maximum-tolerated Dose and Investigate Safety, Pharmacokinetics, and Efficacy of BI 754091 in Patients With Advanced Solid Tumours

The main objective of the dose-escalation part of the trial is to determine the safety and tolerability, and to determine the Maximum Tolerated Dose and/or the Recommended Phase 2 Dose (RP2D) of BI 754091 on the basis of patients with dose-limiting toxicities (DLTs) in patients with selected advanced solid malignancies. Safety and tolerability will be evaluated by monitoring the occurrence of adverse events (AEs), serious AEs (SAE), and laboratory parameter abnormalities, as well as changes to vital signs.

Secondary objectives are the determination of the PK profile of BI 754091 after single and multiple doses of BI 754091, and the preliminary assessment of antitumour activity.

In the dose-expansion part of the trial, the main objectives are to further assess the safety, efficacy, PK profile, and biomarkers of BI 754091 in tumours with specific tumour types and/or genetic mutations at the RP2D.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BI 754091

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre - Hamilton Health Sciences
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
  • Illinois
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provision of signed and dated, written Informed Consent Form (ICF) prior to any trial-specific procedures, sampling, or analyses. If a patient declines to participate in the voluntary pharmacogenetics component of the trial, he/she will not be excluded from other aspects of the trial.
• Patients ≥18 years of age at the time of signature of the ICF

• Phase Ia (dose-escalation)

  • patients with a histologically confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours (any type).
  • patients who have received all therapy known to confer clinical benefit (including anti-PD-1 or anti-PDL1 therapies, if relevant), or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies. Patients with anti- PD-1 or anti-PDL1 experience must have a minimum of 60 days between the last dose of the previous anti PD-1/PD-L1 and Cycle 1 Day 1 of BI 754091 treatment.
  • Patients may agree to provide optional paired biopsies.

• Phase Ib (dose expansion)

  • patients with a histologically confirmed diagnosis of select advanced, unresectable, and/or metastatic solid tumours with either 1) high tumor mutation excluding high microsatellite instability or 2) refractory squamous cell cervical, anal and skin tumors, or 3) recurrent vaginal or vulvar squamous cell carcinoma.
  • All patients must have measurable lesions according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 must have at least 1 tumour lesion amenable to biopsy, and must be medically fit and willing to undergo a biopsy before first treatment and, unless clinically contraindicated, after 6 weeks on therapy
  • patients who are anti-PD-1 and anti-PDL-1naïve but have failed conventional treatment (excluding anti-PD-1 treatment), or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies.
• Eastern Cooperative Oncology Group (ECOG) score: 0 to 1
• Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement

• Females of child-bearing potential willing to use adequate contraceptive measures from the time of screening until 6 months after trial discontinuation, who are not or will not be breast feeding, and agree to have pregnancy tests prior to the start of dosing and at regular visits during the trial. Females not of childbearing potential must have evidence of such by fulfilling one of the following criteria at screening:

  • Post-menopausal: defined as more than 50 years-of-age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
  • Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy
  • Women under 50 years-of-age would be considered postmenopausal if they have been amenorrhoeic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone and luteinizing hormone levels in the postmenopausal range for the institution.
  • For women of childbearing potential using a contraceptive pill, an additional barrier method is necessary. Acceptable highly effective methods of contraception include total sexual abstinence when this is in line with the preferred and usual lifestyle of the study participant (periodic abstinence such as calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception), an intrauterine device or intrauterine hormone-releasing system, bilateral tubal ligation, and vasectomised partner (with post-vasectomy proof of absence of sperm)
• Further inclusion criteria apply

Exclusion criteria:

• Major surgery (major according to the Investigator's assessment) performed within 12 weeks prior to first trial treatment 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 enrolment in this trial
• Any investigational or anti-tumour treatment within 4 weeks or 5 half-life period (whichever is shorter) prior to the initial administration of BI 754091.
• 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-cell carcinoma of the skin, 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 Progression of Disease 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/mm3)
  • Platelet count <100 x 10^9/L
  • Haemoglobin <90 g/L (<9 g/dL)
  • 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
  • Aspartate aminotransferase (AST) >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
  • Total bilirubin >1.5 times ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin >3.0 x ULN or direct bilirubin >1.5 x ULN
  • Creatinine >1.5 times ULN or creatinine clearance <50 mL/min (measured or calculated by Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.

• Any of the following cardiac criteria:

  • Mean resting corrected QT interval (QTc) >470 msec
  • Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting Electrocardiograms, e.g., complete left bundle branch block, third degree heart block
  • 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
  • Ejection fraction (EF) <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.
• History of pneumonitis within the last 5 years
• History of severe hypersensitivity reactions to other monoclonal Antibodies
• Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of BI 754091
• Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy
• Known history of human immunodeficiency virus infection or an active hepatitis B or C virus infection. HIV infection is allowed for patients in cohort 6 (cervical/anal squamous) and cohort 7 (vulvar)
• Interstitial lung disease
• Chronic alcohol or drug abuse or any condition that, in the Investigator's opinion, makes him/her an unreliable trial subject, unlikely to complete the trial, or unable to comply with the protocol procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase Ia dose escalation: Cohort 1; Low dose.	Drug: BI 754091
Experimental: Phase Ia dose escalation: Cohort 2; Medium dose.	Drug: BI 754091
Experimental: Phase Ia dose escalation: Cohort 3; High dose.	Drug: BI 754091
Experimental: Phase Ib dose expansion: Cohort 4; Patients with solid tumours including NSCLC, bladder cancer, melanoma, gastric cancer, ovarian cancer, triple-negative breast cancer, and renal-cell cancer	Drug: BI 754091
Experimental: Phase Ib dose expansion: Cohort 5; Patients with tumours with high TMB excluding those with high microsatellite instability (MSI-high)	Drug: BI 754091
Experimental: Phase Ib dose expansion: Cohort 6; Patients with refractory squamous cell cervical, anal, and skin tumours.	Drug: BI 754091
Experimental: Phase Ib dose escalation: Cohort 7; Patients with recurrent human papillomavirus (HPV)-positive, or HPV-negative, vaginal or vulvar squamous cell carcinoma (VSCC)	Drug: BI 754091

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ia Dose Escalation: Number of Participants With Dose-limiting Toxicities (DLTs) in the First Cycle (3 Weeks)	Number of participants experiencing dose-limiting toxicities (DLTs) graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 / 5.0 observed in the first cycle (3 weeks) in order to meet the objective of assessment of the maximum tolerated dose (MTD) of ezabenlimab.	Up to 3 weeks.
Phase Ib Dose Expansion: Number of Participants With Dose-limiting Toxicities (DLTs) During the Entire Treatment Period	Phase Ib dose expansion: Number of participants with dose-limiting toxicities (DLTs) during the entire treatment period	From first infusion of study treatment until end of study treatment at the time of interim database lock plus 30 days, up to 853 days.
Phase Ib Dose Expansion: Confirmed Objective Response (OR), Defined as the Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST v1.1 as Assessed by the Investigator	Confirmed objective Response (OR), defined as the best overall response of confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 assessed by the Investigator, where the best overall response is the best time point response recorded from the first administration of BI 754091 until the earliest of disease progression according to RECIST v1.1, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow- up or withdrawal of consent.	From first infusion of study treatment until end of study treatment at the time of interim database lock plus 30 days, up to 853 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ia Dose Escalation: Confirmed Objective Response According to RECIST v.1.1 as Assessed by the Investigator	Confirmed OR, defined as the best overall response of confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the Investigator where the best overall response is the best time point response recorded from the first administration of BI 754091 until the earliest of disease progression according to RECIST v1.1, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow- up or withdrawal of consent.	From the first administration of BI 754091 until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow- up or withdrawal of consent, up to 511 days.
Phase Ia Dose Escalation: Maximum Measured Concentration (Cmax) of Ezabenlimab in Plasma	Maximum measured concentration (Cmax) of ezabenlimab in plasma after single or multiple dose administration of ezabenlimab. Results for cycle 1 and cycle 2 are reported.	5 minutes prior to BI 754091 infusion start and 0.5, 1, 1.5, 2, 4, 7, 24, 72, 168 and 336 hours after start of BI 754091 infusion.
Phase Ia Dose Escalation: Area Under the Concentration-time Curve of Ezabenlimab in Plasma Over the Time Interval From 0 to 504 Hours (AUC0-504)	Area under the Concentration-time curve of ezabenlimab in plasma over the time interval from 0 to 504 hours (AUC0-504) after single and multiple dose administrations of ezabenlimab. Results for cycle 1 and cycle 2 are reported.	5 minutes prior to BI 754091 infusion start and 0.5, 1, 1.5, 2, 4, 7, 24, 72, 168, 336 and 504 hours after start of BI 754091 infusion.
Phase Ia Dose Escalation: Number of Participants Experiencing Dose-limiting Toxicities (DLTs) From the Start of Treatment Until End of Treatment	Number of participants experiencing dose-limiting toxicities (DLTs), graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 / 5.0, from the start of treatment until end of treatment (in all cycles) as assessed approximately every 3 weeks.	From first infusion of study treatment until the last infusion of study treatment plus 30 days, up to 511 days.
Phase Ib Dose Expansion: Confirmed Progression-free Survival (PFS) Defined From Date of Start of Ezabenlimab to the Date of Disease Progression or Death, Whichever Was Earlier, According to RECIST v1.1 as Assessed by the Investigator	Confirmed Progression-free survival (PFS) defined from date of start administration of BI 754091 to the date of disease progression according to RECIST v1.1 as assessed by the Investigator or death from any cause, whichever is earlier. PFS according to RECIST v1.1: For patients with 'event' as outcome for PFS: - PFS [days] = date of outcome - date of first treatment administration + 1 For patients with 'censored' as outcome for PFS: - PFS (censored) [days] = date of outcome - date of first treatment administration+ 1 Median progression free survival time in months is reported.	From first BI 754091 infusion until disease progression or death, whichever is earlier up to 1668 days.
Phase Ib Dose Expansion: Percentage of Participants With Adverse Events (AEs)	Percentage of participants with adverse events (AEs)	From first infusion of study treatment until end of study treatment plus 30 days, up to 1668 days.
Phase Ib Dose Expansion: Percentage of Participants With Serious Adverse Events (SAEs)	Percentage of participants with serious adverse events (SAEs).	From first infusion of study treatment until end of study treatment at the time of interim database lock plus 30 days, up to 853 days.
Phase Ib Dose Expansion: Percentage of Participants With Clinically Relevant Abnormalities in Laboratory Evaluations	Percentage of participants with clinically relevant abnormalities in laboratory evaluations is reported by the percentage of participants with liver enzyme elevations. Abbreviations: ALT: Alanine aminotransferase ALP: Alkaline Phosphatase AST: Aspartate aminotransferase ULN: Upper limit of normal *: Tbili elevation must be within +/- 30 days of ALT and/or AST elevation	From first infusion of study treatment until end of study treatment plus 30 days, up to 1668 days.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2016
• Primary Completion (Actual): April 30, 2021
• Study Completion (Actual): August 1, 2023

Study Registration Dates

• First Submitted: October 31, 2016
• First Submitted That Met QC Criteria: October 31, 2016
• First Posted (Estimated): November 2, 2016

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 1381.1; 2017-005043-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

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