Clinical trial NCT05916313: A Study to Test How Well Different Doses of BI 764532 Are Tolerated by People With a Tumour in the Brain That is Positive for DLL3
Official title: A Phase Ib Open-label, Multi-center, Dose Escalation Trial of BI 764532 Given as Monotherapy Administered by Repeated Intravenous Infusions in Patients With Glioma Expressing DLL3
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Glioma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2023-06-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study (1438-0003) is open to adults with a tumour in the brain that is positive for the tumour marker delta-like 3 (DLL3). This study is in people with advanced cancer for whom previous treatment was not successful.

The purpose of this study is to find out the highest dose of BI 764532 that people with a brain tumour that is positive for DLL3 can tolerate. BI 764532 is an antibody-like molecule that can attach and link together the cancer cells and T-cells of the immune system (DLL3/CD3 bispecific). This may help the immune system fight cancer.

Participants get BI 764532 infusions into a vein when starting treatment. If there is benefit for the participants and if they can tolerate it, the treatment is continued. During this time, participants visit the study site at regular intervals. The total number of visits depends on how they respond to and tolerate the treatment. The first study visits include staying to monitor participants' safety. Doctors record any unwanted effects and regularly check the general health of the participants.


Eligibility criteria: Inclusion Criteria:

1. Male or female participants ≥18 years old and at least at the legal age of consent in countries where it is greater than 18 years at the time of signature of the first informed consent form (ICF1).
2. Signed and dated written informed consent (ICF1 and ICF2) in accordance with International Council for Harmonisation-Good clinical practice (ICH-GCP) and local legislation prior to admission to the trial.
3. Patients with histologically confirmed primary progressive diffuse glioma who have failed standard of care therapies.
4. Availability of archival tumour tissue for Delta-like 3 (DLL3) expression by central assessment.
5. Tumours must be positive for DLL3 expression by immunohistochemistry (IHC) on archived tumour tissue according to central pathology review.
6. Documented unequivocal progression after radiotherapy and/or chemotherapy with measurable disease by response assessment in neuro-oncology (RANO) criteria.
7. Karnofsky performance score ≥70. Further inclusion criteria apply.

Exclusion Criteria:

1. Previous treatment in this trial.
2. Current enrolment in another investigational device or drug trial.
3. Presence of extracranial metastatic or leptomeningeal disease.
4. Previous treatment with therapies targeting DLL3.
5. Prior treatment with bevacizumab or other anti-vascular endothelial growth factor (anti-VEGF) or anti-angiogenic treatment within 6 months prior to first administration of BI 764532.
6. Recent anti-cancer therapy: treatment with any other anticancer drug within 21 days or within 5 half-life periods (whichever is shorter) prior to first administration of BI 764532.
7. Radiotherapy within the 3 months prior to the diagnosis of progression; unless tumour progression is clearly outside the radiation field or tumour progression is unequivocally proven by surgery/biopsy.

Further exclusion criteria apply.

Primary outcomes:
measure: Part A: Occurrence of dose-limiting toxicity (DLT) during the maximum tolerated dose (MTD) evaluation period
timeFrame: up to 4 weeks
Secondary outcomes:
measure: Part A: Occurrence of dose-limiting toxicity (DLT) during the entire treatment period
timeFrame: up to 26 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Salzburg
country: Austria
facility: Salzburg Cancer Research Institute
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: München
country: Germany
facility: Klinikum der Universität München AÖR
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum-ROTTERDAM-50697
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Aarau
country: Switzerland
facility: Cantonal Hospital of Aarau
city: Lausanne
country: Switzerland
facility: University Hospital of Lausanne
city: Zurich
country: Switzerland
facility: University Hosp. Zurich
Study officials:
References: