This Study Tests How BI 754111 is Distributed in Patients With Advanced Non-small Cell Lung Cancer or Patients With Head and Neck Cancer Who Are Treated With BI 754091

NCT03780725 | Terminated Phase 1 Results

• 2 other identifiers: 1381-00032017-005046-30
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of this study is to determine the biodistribution and intra-tumor accumulation of \[89Zr\]Zr-BI 754111 at baseline and its change upon treatment

Conditions

Head and Neck Neoplasms; Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (2)

• Standard Uptake Value (SUV) in a 1ml Sphere Around Highest SUV Pixel (SUVpeak) of [89Zr]Zr-BI 754111 for Tumor Uptake - Part 1

  The standardized uptake values (SUVs) are calculated as the ratios of the image derived radioactivity concentration upon the whole body concentration of the injected radioactivity, i.e. image derived radioactivity concentration / injected radioactivity concentration upon the whole body - a unitless value since the unit has been cancelled out. The Standard uptake value (SUV) in a 1 milliliter (mL) sphere around highest SUV pixel (SUVpeak) of \[89Zr\]Zr-BI 754111 for tumor uptake for part 1 participants is reported. The SUVpeak (also unitless since it is a SUV value) is summarized for each imaging time point (96hour, 144hour) as the mean tumor uptake over all selected lesions for each treatment cycle, respectively.

  At 96 hours and 144 hours post-injection of [89Zr]Zr-BI 754111 in each cycle.

• Standard Uptake Value (SUV) in a 1ml Sphere Around Highest SUV Pixel (SUVpeak) of [89Zr]Zr-BI 754111 for Tumor Uptake - Part 2

  The standardized uptake values (SUVs) are calculated as the ratios of the image derived radioactivity concentration upon the whole body concentration of the injected radioactivity, i.e. image derived radioactivity concentration / injected radioactivity concentration upon the whole body - a unitless value since the unit has been cancelled out. The Standard uptake value (SUV) in a 1 milliliter (mL) sphere around highest SUV pixel (SUVpeak) of \[89Zr\]Zr-BI 754111 for tumor uptake for part 2 participants is reported. The SUVpeak (also unitless since it is a SUV value) is summarized for each imaging time point (96hour, 144hour) as the mean tumor uptake over all selected lesions for each treatment cycle, respectively.

  At 96 hours and 144 hours post-injection of [89Zr]Zr-BI 754111 in each cycle.

Study Arms (2)

Part 1: Ezabenlimab 240mg + BI 754111 600mg

EXPERIMENTAL

Drug: BI 754111; Drug: [89Zr]Zr-BI 754111; Drug: BI 754091

Part 2: Ezabenlimab 240mg + BI 754111 40mg

EXPERIMENTAL

Drug: BI 754111; Drug: [89Zr]Zr-BI 754111; Drug: BI 754091

Interventions

BI 754111 DRUG

Solution for infusion

Part 1: Ezabenlimab 240mg + BI 754111 600mg; Part 2: Ezabenlimab 240mg + BI 754111 40mg

[89Zr]Zr-BI 754111 DRUG

Solution for infusion

Part 1: Ezabenlimab 240mg + BI 754111 600mg; Part 2: Ezabenlimab 240mg + BI 754111 40mg

BI 754091 DRUG

Solution for infusion

Also known as: Ezabenlimab

Part 1: Ezabenlimab 240mg + BI 754111 600mg; Part 2: Ezabenlimab 240mg + BI 754111 40mg

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
• Patients of legal age (according to local legislation) at the time of signature of the ICF
• Patients with histologically confirmed diagnosis of recurrent NSCLC who received anti- PD-1 or anti PD-L1 as Part of last treatment with at least 3 months of stable disease (i.e.patients with confirmed response (PR or CR) regardless of duration of response or stable disease (SD) for a minimum of 3 months) and have become refractory to anti-PD- 1/ anti-PD-L1 based treatment OR
• Patients with histologically confirmed diagnosis of recurrent metastatic HNSCC who progressed after platinum based therapy or not indicated for receiving standard (radio) chemotherapy (previous treatment with anti- PD-1/ PD-L1 is allowed)
• Eastern Cooperative Oncology Group (ECOG, R01-0787) score: 0 to 1
• Patient must have at least one PET imageable and evaluable tumor lesion of 20mm
• Patients must have at least one tumor lesion amenable to biopsy. This lesion should be PET imageable and evaluable as defined above and the biopsy should be obtained before first BI 754091 administration, unless medically contra-indicated. In the latter case, 25 4μm sections from an archival biopsy taken at relapse after the previous treatment are acceptable
• Must have evaluable lesion(s) according to Revised Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and iRECIST
• Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement
• Male or female patients. Women of childbearing potential (WOCBP)1 and men able to father a child must be ready and able to use highly effective methods of birth control per International Conference on Harmonisation (ICH) M3 (R2) (that result in a low failure rate of less than 1% per year when used consistently and correctly) during trial Participation and for at least 6 months after the last administration of trial medication. A list of contraception methods meeting these criteria is provided in the patient information.

You may not qualify if:

• Not having fully recovered from major surgery before they enter into the trial according to investigator judgment or planned for major surgery 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
• Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled
• Previous treatment in this trial
• Any investigational or anti-tumor treatment within 4 weeks or within 5 half-life periods (whichever is shorter) prior to the initiation of trial treatment.
• Any unresolved toxicities from prior therapy greater than 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
• Prior treatment with anti-LAG-3 agents
• 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 tumors 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 laboratory values
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \>470 msec
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECGs, 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 \<55% or the lower limit of normal of the institutional standard.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Amsterdam UMC Locatie VUMC

Amsterdam, 1081HV, Netherlands

Location

Related Publications (1)

• Miedema IHC, Huisman MC, Zwezerijnen GJC, Grempler R, Pitarch AP, Thiele A, Hesse R, Elgadi M, Peltzer A, Vugts DJ, van Dongen GAMS, de Gruijl TD, Menke-van der Houven van Oordt CW, Bahce I. 89Zr-immuno-PET using the anti-LAG-3 tracer [89Zr]Zr-BI 754111: demonstrating target specific binding in NSCLC and HNSCC. Eur J Nucl Med Mol Imaging. 2023 Jun;50(7):2068-2080. doi: 10.1007/s00259-023-06164-w. Epub 2023 Mar 2.

  PMID: 36859619 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

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

Model Details: The trial is divided in 2 Parts and will be conducted in a staggered approach, i.e. Part 2 follows Part 1. Part 2 will be initiated following a positive decision of the Study Monitoring Committee (SMC) after reviewing of all available data from Part 1 in order to assess whether a blockade of \[89Zr\]Zr-BI 754111 will be demonstrated.

Study Record Dates

• First Submitted: November 26, 2018
• First Posted: December 19, 2018
• Study Start: January 22, 2019
• Primary Completion: February 19, 2020
• Study Completion: December 8, 2020
• Last Updated: January 13, 2026
• Results First Posted: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)