Small Cell Lung CancerLarge Cell Neuroendocrine Lung CarcinomaExtrapulmonary Neuroendocrine Carcinoma of Small Cell HistologyExtrapulmonary Neuroendocrine Carcinoma of Large Cell Histology
Investigational drug(s) / intervention(s)
ObrixtamigZL-1310Atezolizumab
Obrixtamig: Obrixtamig
ZL-1310: ZL-1310
Atezolizumab: Atezolizumab
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion criteria:
For Part 1
1. Diagnosed with locally advanced, metastatic or relapsed cancer of the following histologies:
* Small cell lung carcinoma (SCLC)
* Large cell neuroendocrine lung carcinoma (LCNEC-L)
* Extrapulmonary neuroendocrine carcinoma (epNEC) of small or large cell histology
2. Patients with tumours with mixed histologies for any above type are eligible only if the neuroendocrine carcinoma/small cell component is predominant and represents at least 50% of the overall tumour tissue
3. Patients for whom no therapy of proven efficacy exists or who are not eligible for established treatment options. Patients must have exhausted available treatment options known to prolong survival for their disease. Previous therapies should include at least one line of platinum-based chemotherapy, unless there is a documented medical reason not to use platinum
For Part 2
4. Histologically or cytologically confirmed extended stage small cell lung cancer (ES-SCLC) (excluding combined histologies) using the American Joint Committee on Cancer (AJCC) tumour node metastasis staging system combined with Veterans Administration Lung Study Group (VALG)'s two stage classification scheme.
5. Patients must have received no prior systemic therapy for ES-SCLC. Participants with prior chemoradiotherapy for Limited stage small cell lung cancer (LS-SCLC) must have been treated with curative intent and had a treatment-free interval of at least 6 months after the last chemotherapy, radiotherapy, or chemoradiotherapy before diagnosis of ES-SCLC to be eligible
For both Part 1 and Part 2
6. Signed and dated written informed consent in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses
7. 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 informed consent form (ICF)
8. Willing and able to comply with scheduled visits, treatment schedule, the planned trial assessments, laboratory tests, restrictions regarding prohibited medications, lifestyle restrictions, and other requirements related to the trial. This includes that they are able to understand and follow trial-related instructions
9. Further inclusion criteria apply.
Exclusion criteria:
1. Serious concomitant disease or medical condition such as neurologic, psychiatric (including substance use disorder), active ulcers (gastrointestinal tract or skin) or laboratory abnormalities that may negatively impact patient safety during trial participation, affect compliance with trial requirements or invalidate assessments relevant for the investigation of the safety and preliminary efficacy of the investigational drugs
2. Patients with a diagnosis of Merkel cell carcinoma or medullary thyroid cancer
3. Presence of leptomeningeal disease and/or carcinomatous meningitis
4. Known hypersensitivity to the trial drugs or their excipients, prior severe, life-threatening hypersensitivity reaction(s) to monoclonal antibodies, or significant risk of allergic or anaphylactic reaction(s) to any of the investigated drug products according to the investigator's judgement
5. Participants who experienced severe, life-threatening immune-mediated adverse events, e.g. serious Grade 3 or higher immune-related adverse event (imAE) or infusion-related reactions, that led to permanent discontinuation while on treatment with immuno-oncology agents
6. Persistent toxicity from previous treatments that has not resolved to ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (except for alopecia, asthenia/fatigue, amenorrhea/menstrual disorders, CTCAE Grade 2 peripheral neuropathy, and CTCAE Grade 2 endocrinopathies controlled by replacement therapy, and toxicities, which are considered irreversible but stable for at least 4 weeks, per investigator judgment)
7. Therapy with any of the following types of treatments or drugs within the noted time intervals prior to IMP administration: At any time: treatment with delta-like ligand 3 (DLL3)-targeting therapies or received more than 30 Gy of thoracic radiotherapy.
8. Prior organ or tissue allograft
9. Further exclusion criteria apply.
Primary outcome measure(s)
Part 1: The occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period — 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 — Up to 24 months.
Part 2: PFS rate at 6 months — 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.
Trial sites (26)
Facility
City
Region
Status
MedStar Georgetown University Hospital
Washington D.C.
District of Columbia
H. Lee Moffitt Cancer Center and Research Institute
Tampa
Florida
University of Kentucky Medical Center
Lexington
Kentucky
Chris Obrien Lifehouse
Camperdown
New South Wales
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
CTR Leon Berard
Lyon
France
HOP Timone
Marseille
France
Institut Gustave Roussy
Villejuif
France
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz
Germany
Robert Bosch Gesellschaft für medizinische Forschung mbH
Stuttgart
Germany
Hokkaido Cancer Center
Hokkaido, Sapporo
Japan
St. Marianna University Hospital
Kanagawa, Kawasaki
Japan
Kansai Medical University Hospital
Osaka, Hirakata
Japan
Shizuoka Cancer Center
Shizuoka, Sunto-gun
Japan
Amsterdam UMC Locatie VUMC
Amsterdam
Netherlands
Szpital Specjalistyczny W Brzozowie Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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