Clinical trial NCT04147234: 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)
Official title: Phase I, First in Human Trial Evaluating BI 1387446 Alone and in Combination With Ezabenlimab (BI 754091) in Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2019-11-01
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 \< 50% measured by echocardiography or Multigated Acquisition (MUGA) scan
* Mean resting corrected QT interval (QTc) \>470 msec
* Further exclusion criteria apply

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) Based on Number of Dose-limiting Toxicities (DLTs)
timeFrame: From first administration of BI 1387446 until to end of treatment cycle 1 (up to 3 weeks).
measure: Number of Patients With DLT in the MTD Evaluation Period
timeFrame: From first administration of BI 1387446 until to end of treatment cycle 1 (up to 3 weeks).
Secondary outcomes:
measure: Objective Response Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)
timeFrame: From start of treatment up to the earliest of progression, death or end of trial (up to 1 year).
measure: Objective Response Based on Response Criteria for Intratumoural Immunotherapy in Solid Tumours (itRECIST)
timeFrame: From start of treatment up to the earliest of progression, death or end of trial (approximately 1 year).
measure: Best Percentage Change From Baseline in Size of Injected Lesions (CTP Version 1 or 2)
timeFrame: From start of treatment up to the earliest of progression, death or end of trial (approximately 1 year).
measure: Best Percentage Change From Baseline in Size of Injected Target Lesions (CTP v3.0 or Later Versions)
timeFrame: From start of treatment up to the earliest of progression, death or end of trial (approximately 1 year).
measure: Best Percentage Change From Baseline in Size of Target Lesions (CTP Version 1 or 2)
timeFrame: From start of treatment until the earliest of progression, death or end of trial (approximately 1 year).
measure: Best Percentage Change From Baseline in Size of Non-injected Target Lesions (CTP v3.0 or Later Versions)
timeFrame: From start of treatment until the earliest of progression, death or end of trial (approximately 1 year).
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Milwaukee
country: United States
facility: Froedtert and The Medical College of Wisconsin
state: Wisconsin
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: CIO Clara Campal
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: London
country: United Kingdom
facility: The Royal Marsden Hospital, Chelsea
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital, Sutton
Study officials:
References: