This study is open to adults with advanced small cell lung cancer and other neuroendocrine cancers. The study has 2 parts. The purpose of Part 1 is to find a suitable dose of a combination study treatment, obrixtamig and ZL-1310. The purpose of Part 2 is to see how obrixtamig and ZL-1310 is tolerated when given with another medicine called a checkpoint inhibitor. Another purpose is to check whether the study treatment can stop the cancer from growing and keep it stable. Obrixtamig and ZL-1310 are being developed to help the immune system fight cancer. In Part 1, participants get obrixtamig and ZL-1310. In Part 2, participants get obrixtamig and ZL-1310 with a checkpoint inhibitor. Part 2 is only open to people with advanced small cell lung cancer. All study treatments are given as infusions into a vein. The study does not have a fixed duration. Participants can receive study treatment for up to 2 years if they benefit from treatment and can tolerate it. Participants visit the study site regularly, with some overnight stays required. During this time, doctors regularly check for health problems that could be caused by the study treatment. They also monitor the size of the tumour(s) and take laboratory tests.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
Northwestern University
Chicago, Illinois, United States
University of Kentucky Medical Center
Lexington, Kentucky, United States
Chris Obrien Lifehouse
Camperdown, New South Wales, Australia
Universitair Ziekenhuis Antwerpen
Edegem, Belgium
Universitair Ziekenhuis Gent
Ghent, Belgium
The Affiliated Cancer Hospital, Guangxi Medical University
Nanning, China
Shanghai Chest Hospital
Shanghai, China
Shanghai Pulmonary Hospital
Shanghai, China
...and 17 more locations
Part 1: The occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period
Time frame: 6 weeks from the first administration of study medication.
Part 2: The occurrence of treatment-emergent adverse events (AEs) leading to trial medication discontinuation or dose modification
Time frame: Up to 24 months.
Part 2: PFS rate at 6 months
Progression-free survival (PFS) is defined as the time from first investigational medicinal product (IMP) administration until the earliest date of disease progression according to Response Evaluation Criteria In Solid Tumours (RECIST 1.1) based on investigator assessments or death from any cause, whichever occurs first.
Time frame: At 6 months.
Part 1 and Part 2: Occurrence of treatment-emergent DLTs
Time frame: Up to 24 months.
Part 1 and Part 2: Occurrence of treatment-emergent adverse event of special interest (AESIs)
Time frame: Up to 24 months.
Part 1 and Part 2: Occurrence of treatment-emergent AEs CTCAE Grade ≥3
AEs CTCAE = Adverse events Common Terminology Criteria for Adverse Events
Time frame: Up to 24 months.
Part 1 and Part 2: Objective response (OR)
OR is defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 (based on investigator assessments) from the first IMP administration until the earliest date of disease progression, death, last evaluable tumour assessment before the start of the next line of anti-cancer treatment, loss to follow-up, or withdrawal of consent.
Time frame: Up to 24 months.
Part 1 and Part 2: Duration of response (DoR)
DoR is defined as the time from the first documented objective response (OR) according to RECIST 1.1 until the earliest date of disease progression or death among patients with confirmed objective response based on investigator assessments.
Time frame: Up to 24 months.
Part 1 and Part 2: Disease control (DC)
DC is defined as best overall response of complete response (CR) or partial response (PR) or stable disease (SD) where best overall response is defined according to RECIST version 1.1 based on investigator assessments from the first IMP administration until the earliest date of disease progression, death or last evaluable tumour assessment before start of the next line of anti-cancer treatment, loss to follow-up or withdrawal of consent.
Time frame: Up to 24 months.
Part 1: Progression-free survival (PFS)
PFS is defined as the time from first IMP administration until the earliest date of disease progression according to RECIST 1.1 based on investigator assessments or death from any cause, whichever occurs first.
Time frame: Up to 24 months.
Part 2: Occurrence of DLTs during the DLT evaluation period
Time frame: 6 weeks from the first administration of study medication.
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