DAREON™-5: An Open-label, Multi-center Phase II Dose Selection Trial of Intravenous BI 764532, a DLL3-targeting T Cell Engager, in Patients With Relapsed/Refractory Extensive-stage Small Cell Lung Cancer and in Patients With Other Relapsed/Refractory Neuroendocrine Carcinomas
Summary
This study is open to adults with small cell lung cancer and other neuroendocrine tumours. The study is in people with advanced cancer for whom previous treatment was not successful or no standard treatment exists. The purpose of this study is to find a suitable dose of BI 764532 (also called obrixtamig) that people with advanced cancer can tolerate. 2 different doses of BI 764532 are tested in this study. Another purpose is to check whether BI 764532 can make tumours shrink. BI 764532 is an antibody-like molecule (DLL3/CD3 bispecific) that may help the immune system fight cancer. The study has 3 parts. In Part 1, participants are put into 2 groups randomly, which means by chance. Participants have an equal chance of being in either group. One group gets dose 1 of BI 764532 and the other group gets dose 2 of BI 764532. In Part 2 and Part 3, all participants receive the same dose of BI 764532. Part 2 and Part 3 are open to people with a certain kind of tumour called extrapulmonary neuroendocrine carcinoma. All participants receive BI 764532 as an infusion into a vein when starting treatment. If there is benefit for the participants and if they can tolerate it, the treatment is given up to the maximum duration of the study. During this time, participants visit the study site regularly. The total number of visits depends on how they respond to and tolerate the treatment. The first study visits include an overnight stay to monitor participants´ safety. Doctors record any unwanted effects and regularly check the general health of the participants.
Arms & interventions
- DrugBI 764532, dose 1
BI 764532, dose 1
- DrugBI 764532, dose 2
BI 764532, dose 2
Outcome measures
Primary
Part 1: Objective response (OR), defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR)
according to RECIST v 1.1 by investigator assessment from the date of treatment start until the earliest date of disease progression, death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent.
Time frame: up to 26 months
Part 1: Occurrence of treatment-emergent adverse events (TEAEs) during the on-treatment period
Time frame: up to 26 months
Part 2: Objective response (OR)
Objective response is defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v 1.1 by blinded independent central review from the date of treatment start until the earliest date of disease progression, death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent
Time frame: up to 27 months
Part 3: Occurrence of treatment-emergent adverse events (TEAEs) during the on-treatment period
Time frame: up to 23 months
Part 3: Objective response (OR) by blinded independent central review
Time frame: up to 23 months
Secondary
Part 1: Duration of objective response (DOR) based on investigator assessment
Time frame: up to 26 months
Part 1: Progression-free survival (PFS) based on investigator assessment
Time frame: up to 26 months
Part 1: Disease control (DC), defined as best overall response of CR or PR or stable disease (SD) based on investigator assessment
Time frame: up to 26 months
Part 1, 2, and 3: Overall survival (OS), defined as the time from treatment start until death from any cause
Time frame: up to 26 months
Part 1, 2, and 3: Change from baseline in EORTC QLQ-C30 physical functioning domain score
Time frame: at baseline, at month 26
Part 1, 2, and 3: Change from baseline in EORTC QLQ-C30 role functioning domain score
Time frame: at baseline, at month 26
Part 1, 2, and 3: Occurrence of treatment-emergent AEs leading to study drug discontinuation during the on-treatment period
Time frame: up to 26 months
Part 2 and 3: Duration of objective response (DOR) based on blinded independent central review
Time frame: up to 27 months
Part 2 and 3: Progression-free survival (PFS) based on blinded independent central review
Time frame: up to 27 months
Part 2 and 3: Disease control (DC) based on blinded independent central review
Time frame: up to 27 months
Part 2: Occurrence of treatment-emergent adverse events (TEAEs) during the on-treatment period
Time frame: up to 27 months
Eligibility criteria
Study locations (16)
Infirmary Cancer Care
Mobile, Alabama, 36607
Mayo Clinic-Arizona
Phoenix, Arizona, 85054
Valkyrie Clinical Trials
Los Angeles, California, 90067
University of California San Francisco
San Francisco, California, 94143
Mayo Clinic Cancer Center
Jacksonville, Florida, 32224
University of Miami
Miami, Florida, 33136
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
Indiana University
Indianapolis, Indiana, 46202
University of Kansas Cancer Center
Westwood, Kansas, 66205
University of Kentucky Medical Center
Lexington, Kentucky, 40536
University of Maryland School of Medicine
Baltimore, Maryland, 21201
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Mayo Clinic, Rochester
Rochester, Minnesota, 55905
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016
Montefiore Medical Center
The Bronx, New York, 10461
Virginia Commonwealth University Health- Adult Outpatient Pavilion
Richmond, Virginia, 23219