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)

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04147234
• Other study ID #: 1426-0001
• Secondary ID: 2019-001082-32
• Status: Completed
• Phase: Phase 1
• Start date: March 9, 2020
• Est. completion date: March 21, 2024

Study information

• Verified date: April 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: March 21, 2024
• Est. primary completion date: November 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• BI 1387446
intratumoral injection
• BI 754091
intravenous infusion

Locations

Country	Name	City	State
Spain	Hospital Vall d'Hebron	Barcelona
Spain	CIO Clara Campal	Madrid
Spain	Hospital Clínico de Valencia	Valencia
United Kingdom	The Royal Marsden Hospital, Chelsea	London
United Kingdom	Churchill Hospital	Oxford
United Kingdom	The Royal Marsden Hospital, Sutton	Sutton
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Froedtert and The Medical College of Wisconsin	Milwaukee	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) based on number of Dose-limiting toxicities (DLTs)		3 weeks
Primary	Number of patients with Dose limiting Toxicity (DLT) in the Maximum tolerated dose (MTD) evaluation period		up to 3 weeks
Secondary	Objective response		An average of 1 year
Secondary	Best percentage change from baseline in size of injected target lesions		An average of 1 year
Secondary	Best percentage change from baseline in size of non-injected target lesions		An average of 1 year

External Links

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