A Study to Find the Best Dose of BI 1387446 Alone or in Combination With Ezabenlimab (BI 754091) in Patients With Different Types of Advanced or Metastatic Cancer (Solid Tumors)

Phase I, First in Human Trial Evaluating BI 1387446 Alone and in Combination With Ezabenlimab (BI 754091) in Solid Tumors

This is a study in adults with advanced cancer (solid tumours) in whom previous treatment was not successful. The study tests 2 medicines called BI 1387446 and BI 754091. Both medicines may help the immune system fight cancer. In this study, BI 1387446 is given to humans for the first time.

The purpose of this study is to find out the highest dose of BI 1387446 alone and in combination with BI 754091 the participants can tolerate. BI 1387446 is injected directly into the tumour.

Participants get BI 1387446 injections every week at the beginning and then every 3 weeks.

Some participants get BI 754091 in addition to BI 1387446. BI 754091 is given as an infusion into a vein every 3 weeks.

As long as they benefit from treatment and can tolerate it, participants can stay in the study for up to 2 years and 8 months. During this time, they visit the study site regularly. At these visit, doctors record any unwanted effects. The doctors also regularly check participants' health.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BI 1387446 50 μg; Drug: BI 1387446 100 μg; Drug: BI 1387446 200 μg; Drug: BI 1387446 400 μg; Drug: BI 754091

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Madrid, Spain, 28050
    • CIO Clara Campal
  • Valencia, Spain, 46010
    • Hospital Clinico de Valencia
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital, Chelsea
  • Oxford, United Kingdom, OX3 7LE
    • Churchill Hospital
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden Hospital, Sutton
• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • The University of North Carolina at Chapel Hill
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria

• Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic malignant solid tumor and indication for treatment
• Patient must have exhausted established treatment options known to prolong survival for the malignant disease, or is not eligible for established treatment options.
• Medically fit and willing to undergo all mandatory trial procedures.
• At least one tumor lesion which is suitable for injection (Screening/initial administration), appropriate for the allocated treatment arm, and measurable.
• At least 1 discrete lesion, in addition to the lesion proposed for injection, which is amenable to biopsy and is not located in the brain, mediastinum or pancreas.
• Adequate organ function or bone marrow reserve
• Further inclusion criteria apply

Exclusion criteria:

• Any investigational or antitumour treatment (including antibodies targeting Programmed Cell Death-1 (PD1) - or programmed Death-Ligand 1 (PDL1)) within 4 weeks or 5 half-life periods (whichever is shorter) prior to the initial administration of BI 1387446 or BI 754091.
• Persistent toxicity from previous treatments (including Immune-related Adverse Events (irAEs)) that has not resolved to ≤ Grade 1, except for alopecia, xerostomia, and immunotherapy related endocrinopathies which may be included if clinically stable on hormone supplements or antidiabetic drugs as per Investigator judgement
• History or evidence of active, non-treatment related autoimmune disease, except for endocrinopathies which may be included if clinically stable on hormone supplements or antidiabetic drugs.
• History or evidence of pneumonitis related to prior immunotherapy
• Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 2 weeks prior to the first dose of BI 1387446 or BI 754091.
• The tumor at the projected injection site has a high risk for local complications, e.g. bleeding related to encasement/infiltration of major blood vessels or contact with liver capsule, compression of vital structures in case of swelling of injected lesion, in the opinion of the Investigator.
• Active infection requiring systemic therapy at the start of treatment in the trial, including active viral hepatitis infection or active tuberculosis infection.
• Cardiac insufficiency New York Heart Association (NYHA) III or IV
• Left ventricular ejection fraction < 50% measured by echocardiography or Multigated Acquisition (MUGA) scan
• Mean resting corrected QT interval (QTc) >470 msec
• Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: BI 1387446 50 μg; Participants were administered 50 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. The injection volume depended on tumor diameter.	Drug: BI 1387446 50 μg; Participants received 50 μg BI 1387446 intratumorally based on tumor diameter, on Day 1 of a 21-day cycle. Injections were administered under visual inspection for skin tumors or imaging guidance.
Experimental: Arm A: BI 1387446 100 μg; Participants were administered 100 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. The injection volume depended on tumor diameter.	Drug: BI 1387446 100 μg; Participants received 100 μg BI 1387446 intratumorally based on tumor diameter, on Day 1 of a 21-day cycle. Injections were administered under visual inspection for skin tumors or imaging guidance.
Experimental: Arm A: BI 1387446 200 μg; Participants were administered 200 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. The injection volume depended on tumor diameter.	Drug: BI 1387446 200 μg; Participants received 200 μg BI 1387446 intratumorally based on tumor diameter, on Day 1 of a 21-day cycle. Injections were administered under visual inspection for skin tumors or imaging guidance.
Experimental: Arm A: BI 1387446 400 μg; Participants were administered 400 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. The injection volume depended on tumor diameter.	Drug: BI 1387446 400 μg; Participants received 400 μg BI 1387446 intratumorally based on tumor diameter, on Day 1 of a 21-day cycle. Injections were administered under visual inspection for skin tumors or imaging guidance.
Experimental: Arm B: BI 1387446 50 μg / ezabenlimab 240 mg; Participants were administered 50 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. BI 754091 (ezabenlimab) was administered intravenously at the recommended phase II dose of 240 mg once every 3 weeks. The maximum duration of ezabenlimab treatment was 34 cycles. BI 1387446 injections were preferably performed after completing the ezabenlimab infusion.	Drug: BI 754091; Participants received BI 754091 (ezabenlimab) intravenously at a dose of 240 mg once every 21-day cycle.; Other Names: Ezabenlimab
Experimental: Arm B: BI 1387446 100 μg / ezabenlimab 240 mg; Participants were administered 100 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. BI 754091 (ezabenlimab) was administered intravenously at the recommended phase II dose of 240 mg once every 3 weeks. The maximum duration of ezabenlimab treatment was 34 cycles. BI 1387446 injections were preferably performed after completing the ezabenlimab infusion.	Drug: BI 754091; Participants received BI 754091 (ezabenlimab) intravenously at a dose of 240 mg once every 21-day cycle.; Other Names: Ezabenlimab
Experimental: Arm B: BI 1387446 200 μg / ezabenlimab 240 mg; Participants were administered 200 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. BI 754091 (ezabenlimab) was administered intravenously at the recommended phase II dose of 240 mg once every 3 weeks. The maximum duration of ezabenlimab treatment was 34 cycles. BI 1387446 injections were preferably performed after completing the ezabenlimab infusion.	Drug: BI 754091; Participants received BI 754091 (ezabenlimab) intravenously at a dose of 240 mg once every 21-day cycle.; Other Names: Ezabenlimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) Based on Number of Dose-limiting Toxicities (DLTs)	The MTD in each arm is defined as the highest dose that is expected to cause less than 25% risk of the true DLT rate being above or equal to 33% during the MTD evaluation period. Estimation of the MTD will be based upon the estimation of the posterior probability of the incidence of DLT in toxicity categories during the MTD evaluation period for all evaluable participants. The MTD evaluation period is defined as the time from the first administration of any trial medication to the start of the second treatment cycle. Specifically, this is the time from the first dose to either the second administration of ezabenlimab or the fourth administration of BI 1387446, whichever occurs first. If the second dose of ezabenlimab or the fourth dose of BI 1387446 is not given, the evaluation period ends 90 days after the last administration.	From first administration of BI 1387446 until to end of treatment cycle 1 (up to 3 weeks).
Number of Patients With DLT in the MTD Evaluation Period	The MTD evaluation period is defined as the time from the first administration of any trial medication to the start of the second treatment cycle. Specifically, this is the time from the first dose to either the second administration of ezabenlimab or the fourth administration of BI 1387446, whichever occurs first. If the second dose of ezabenlimab or the fourth dose of BI 1387446 is not given, the evaluation period ends 90 days after the last administration.	From first administration of BI 1387446 until to end of treatment cycle 1 (up to 3 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)	Objective response, as defined by the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1), in accordance with Clinical Trial Protocol (CTP) Version 1 and 2, will be presented in terms of the objective response rate (ORR). The ORR is the proportion of patients whose best overall response is a confirmed complete response (CR) or partial response (PR). This determination is based on the investigator's assessment according to RECIST 1.1 criteria, from the date of the first treatment administration until the earliest occurrence of any of the following events: disease progression, death, the last evaluable tumor assessment before the initiation of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent. Cross-over patients are shown in both Arm A (reflecting their initial treatment) and Arm B (reflecting their first treatment post-crossover). Their best overall response is counted, regardless of whether it occurred before or after the crossover.	From start of treatment up to the earliest of progression, death or end of trial (up to 1 year).
Objective Response Based on Response Criteria for Intratumoural Immunotherapy in Solid Tumours (itRECIST)	Objective Response based on Response Criteria for Intratumoural Immunotherapy in Solid Tumours (itRECIST): (CTP version 3 and later) Objective response (OR) by itRECIST will be presented in terms of objective response rate (ORR), which is defined as the rate of patients whose best overall response is confirmed itCR or itPR as determined by the Investigator's assessment according to itRECIST from date of first treatment administration until the earliest of confirmed disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up or withdrawal of consent. Cross-over patients are shown in both Arm A (reflecting their initial treatment) and Arm B (reflecting their first treatment post-crossover). Their best overall response is counted, regardless of whether it occurred before or after the crossover.	From start of treatment up to the earliest of progression, death or end of trial (approximately 1 year).
Best Percentage Change From Baseline in Size of Injected Lesions (CTP Version 1 or 2)	This endpoint evaluated the best percentage change (i.e., greatest reduction) in the size of injected lesions from baseline (the first measurement at the start of treatment) over time. The best percentage change from baseline in the size of injected lesions was analyzed using descriptive statistics. All lesion measurements recorded from the start of trial treatment until the earliest of the following were considered: disease progression (assessed under CTP v1 and v2 using RECIST 1.1), initiation of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent. Cross-over patients appear in both Arm A (initial treatment) and Arm B (post-crossover treatment). Their best overall response is counted, regardless of timing. Negative values indicate a reduction in injected lesion diameters; positive values indicate an increase.	From start of treatment up to the earliest of progression, death or end of trial (approximately 1 year).
Best Percentage Change From Baseline in Size of Injected Target Lesions (CTP v3.0 or Later Versions)	This endpoint evaluated the best percentage change (i.e., greatest reduction) in the size of injected target lesions from baseline (the first measurement at the start of treatment) over time. The best percentage change from baseline in the size of injected target lesions was analyzed using descriptive statistics. All lesion measurements recorded from the start of trial treatment until the earliest of the following were considered: disease progression (assessed under CTP version 3 and later using itRECIST), initiation of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent. Negative values indicate reduced lesion diameters; positive values indicate increases. Cross-over patients are included in Arm A (initial treatment) and Arm B (first post-crossover treatment), with their best response counted regardless of timing.	From start of treatment up to the earliest of progression, death or end of trial (approximately 1 year).
Best Percentage Change From Baseline in Size of Target Lesions (CTP Version 1 or 2)	This endpoint evaluated the best percentage change (i.e., greatest reduction) in the size of target lesions from baseline (the first measurement at the start of treatment) over time. The best percentage change from baseline in the size of target lesions was analyzed using descriptive statistics. All lesion measurements recorded from the start of trial treatment until the earliest of the following were considered: disease progression (assessed under CTP v1 and v2 using RECIST 1.1), initiation of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent. Cross-over patients appear in both Arm A (initial treatment) and Arm B (post-crossover treatment). Their best overall response is counted, regardless of timing. Negative values indicate a reduction in lesion diameters; positive values indicate an increase.	From start of treatment until the earliest of progression, death or end of trial (approximately 1 year).
Best Percentage Change From Baseline in Size of Non-injected Target Lesions (CTP v3.0 or Later Versions)	This endpoint evaluated the best percentage change (i.e., greatest reduction) in the size of non-injected target lesions from baseline (the first measurement at the start of treatment) over time. The best percentage change from baseline in the size of non-injected target lesions was analyzed using descriptive statistics. All lesion measurements recorded from the start of trial treatment until the earliest of the following were considered: disease progression (assessed under CTP version 3 and later using itRECIST), initiation of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent.	From start of treatment until the earliest of progression, death or end of trial (approximately 1 year).

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2020
• Primary Completion (Actual): November 15, 2022
• Study Completion (Actual): March 21, 2024

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: October 30, 2019
• First Posted (Actual): November 1, 2019

Study Record Updates

• Last Update Posted (Actual): August 19, 2025
• Last Update Submitted That Met QC Criteria: August 18, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 1426-0001; 2019-001082-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.
• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No