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)

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Neoplasms

Treatments: Drug: BI 1387446 50 μg; Drug: BI 1387446 200 μg; Drug: BI 754091; Drug: BI 1387446 400 μg; Drug: BI 1387446 100 μg

Study type: Interventional

Funder types: Industry

Identifiers

NCT04147234

2019-001082-32 (EudraCT Number)

1426-0001

Details and patient eligibility

About

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.

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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42 participants in 7 patient groups

Arm A: BI 1387446 50 μg

Experimental group

Description:

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.

Treatment:

Drug: BI 1387446 50 μg

Arm A: BI 1387446 100 μg

Experimental group

Description:

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.

Treatment:

Drug: BI 1387446 100 μg

Arm A: BI 1387446 200 μg

Experimental group

Description:

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.

Treatment:

Drug: BI 1387446 200 μg

Arm A: BI 1387446 400 μg

Experimental group

Description:

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.

Treatment:

Drug: BI 1387446 400 μg

Arm B: BI 1387446 50 μg / ezabenlimab 240 mg

Experimental group

Description:

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.

Treatment:

Drug: BI 754091

Arm B: BI 1387446 100 μg / ezabenlimab 240 mg

Experimental group

Description:

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.

Treatment:

Drug: BI 754091

Arm B: BI 1387446 200 μg / ezabenlimab 240 mg

Experimental group

Description:

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.

Treatment:

Drug: BI 754091