Phase 1
Completed N=38
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
Source: ClinicalTrials.gov NCT04147234 ↗
Enrolled (actual)
38
Serious AEs
42.9%
Results posted
Jun 2025
Primary outcomePrimary: Maximum Tolerated Dose (MTD) Based on Number of Dose-limiting Toxicities (DLTs) — NA; NA μg (microgram)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) Based on Number of Dose-limiting Toxicities (DLTs) |
NA; NA | — |
| PRIMARY Number of Patients With DLT in the MTD Evaluation Period |
0; 0; 1; 0; 0; 0 | — |
| SECONDARY Objective Response Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) |
0; 0; 0; 0; 0 | — |
| SECONDARY Objective Response Based on Response Criteria for Intratumoural Immunotherapy in Solid Tumours (itRECIST) |
0; 1; 0; 1 | — |
| SECONDARY Best Percentage Change From Baseline in Size of Injected Lesions (CTP Version 1 or 2) |
23.36; -20.73; -2.78; 0.54; 13.33 | — |
| SECONDARY Best Percentage Change From Baseline in Size of Injected Target Lesions (CTP v3.0 or Later Versions) |
-6.67; -37.76; -17.43; -16.93 | — |
| SECONDARY Best Percentage Change From Baseline in Size of Target Lesions (CTP Version 1 or 2) |
-0.07; 1.02; -0.10; 0.07; 0.25 | — |
| SECONDARY Best Percentage Change From Baseline in Size of Non-injected Target Lesions (CTP v3.0 or Later Versions) |
-6.23; 1.30; 13.42; -17.28 | — |
Eligibility 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 470 msec
- Further exclusion criteria apply
Data sourced from ClinicalTrials.gov (NCT04147234). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.