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

NCT02952248 | Completed Phase 1 Results

• 2 other identifiers: 1381.12017-005043-33
• Study Type: interventional
• Target: 110
• Locations: 3 countries
• Sites: 13

Brief Summary

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.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• Phase Ia Dose Escalation: Confirmed Objective Response According to RECIST v.1.1 as Assessed by the Investigator

  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

  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)

  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

  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

  From first BI 754091 infusion until disease progression or death, whichever is earlier up to 1668 days.

Study Arms (7)

Phase Ia dose escalation: Cohort 1

EXPERIMENTAL

Low dose.

Drug: BI 754091

Phase Ia dose escalation: Cohort 2

EXPERIMENTAL

Medium dose.

Drug: BI 754091

Phase Ia dose escalation: Cohort 3

EXPERIMENTAL

High dose.

Drug: BI 754091

Phase Ib dose expansion: Cohort 4

EXPERIMENTAL

Patients with solid tumours including NSCLC, bladder cancer, melanoma, gastric cancer, ovarian cancer, triple-negative breast cancer, and renal-cell cancer

Drug: BI 754091

Phase Ib dose expansion: Cohort 5

EXPERIMENTAL

Patients with tumours with high TMB excluding those with high microsatellite instability (MSI-high)

Drug: BI 754091

Phase Ib dose expansion: Cohort 6

EXPERIMENTAL

Patients with refractory squamous cell cervical, anal, and skin tumours.

Drug: BI 754091

Phase Ib dose escalation: Cohort 7

EXPERIMENTAL

Patients with recurrent human papillomavirus (HPV)-positive, or HPV-negative, vaginal or vulvar squamous cell carcinoma (VSCC)

Drug: BI 754091

Interventions

BI 754091 DRUG

Phase Ia dose escalation: Cohort 1; Phase Ia dose escalation: Cohort 2; Phase Ia dose escalation: Cohort 3; Phase Ib dose escalation: Cohort 7; Phase Ib dose expansion: Cohort 4; Phase Ib dose expansion: Cohort 5; Phase Ib dose expansion: Cohort 6

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (13)

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Greenville Health System

Greenville, South Carolina, 29605, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Juravinski Cancer Centre - Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, H2X 0A9, Canada

Location

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

The Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2016
• First Posted: November 2, 2016
• Study Start: November 21, 2016
• Primary Completion: April 30, 2021
• Study Completion: August 1, 2023
• Last Updated: January 27, 2026
• Results First Posted: January 27, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); CA (4); GB (2)