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)

NCT04147234 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 1426-00012019-001082-32
• Study Type: interventional
• Target: 42
• Locations: 3 countries
• Sites: 8

Brief Summary

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.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Objective Response Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)

  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)

  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)

  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)

  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)

  From start of treatment until the earliest of progression, death or end of trial (approximately 1 year).

Study Arms (7)

Arm A: BI 1387446 50 μg

EXPERIMENTAL

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

Arm A: BI 1387446 100 μg

EXPERIMENTAL

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

Arm A: BI 1387446 200 μg

EXPERIMENTAL

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

Arm A: BI 1387446 400 μg

EXPERIMENTAL

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

Arm B: BI 1387446 50 μg / ezabenlimab 240 mg

EXPERIMENTAL

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

Arm B: BI 1387446 100 μg / ezabenlimab 240 mg

EXPERIMENTAL

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

Arm B: BI 1387446 200 μg / ezabenlimab 240 mg

EXPERIMENTAL

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

Interventions

BI 1387446 50 μg DRUG

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.

Arm A: BI 1387446 50 μg

BI 754091 DRUG

Participants received BI 754091 (ezabenlimab) intravenously at a dose of 240 mg once every 21-day cycle.

Also known as: Ezabenlimab

Arm B: BI 1387446 100 μg / ezabenlimab 240 mg; Arm B: BI 1387446 200 μg / ezabenlimab 240 mg; Arm B: BI 1387446 50 μg / ezabenlimab 240 mg

BI 1387446 100 μg DRUG

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.

Arm A: BI 1387446 100 μg

BI 1387446 200 μg DRUG

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.

Arm A: BI 1387446 200 μg

BI 1387446 400 μg DRUG

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.

Arm A: BI 1387446 400 μg

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (8)

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Froedtert and The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

CIO Clara Campal

Madrid, 28050, Spain

Location

Hospital Clínico de Valencia

Valencia, 46010, Spain

Location

The Royal Marsden Hospital, Chelsea

London, SW3 6JJ, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

The Royal Marsden Hospital, Sutton

Sutton, SM2 5PT, 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

018002430127

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2019
• First Posted: November 1, 2019
• Study Start: August 3, 2020
• Primary Completion: November 15, 2022
• Study Completion: March 21, 2024
• Last Updated: August 19, 2025
• Results First Posted: June 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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'.

Locations

ES (3); GB (3); US (2)