DAREON®-36: A Study to Test Obrixtamig in Combination With ZL-1310 in People With Advanced Small Cell Lung Cancer or Other Neuroendocrine Cancers

Official title

A Phase Ib/II, Open-label, Safety and Tolerability Trial of Obrixtamig in Combination With ZL-1310 in Patients With Poorly Differentiated NEC

Overview

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.

Interventions

• Drug Obrixtamig
  Obrixtamig
• Drug ZL-1310
  ZL-1310
• Drug Atezolizumab
  Atezolizumab

Primary outcome measures

• 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 [Time frame: At 6 months.]

Secondary outcome measures (8)

• 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 [Time frame: Up to 24 months.]
• Part 1 and Part 2: Objective response (OR) [Time frame: Up to 24 months.]
• Part 1 and Part 2: Duration of response (DoR) [Time frame: Up to 24 months.]
• Part 1 and Part 2: Disease control (DC) [Time frame: Up to 24 months.]
• Part 1: Progression-free survival (PFS) [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.]

Eligibility criteria

Inclusion criteria

For Part 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
• 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
• 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

• 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.
• 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

• 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
• 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)
• 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
• Further inclusion criteria apply.

Exclusion criteria

• 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
• Patients with a diagnosis of Merkel cell carcinoma or medullary thyroid cancer
• Presence of leptomeningeal disease and/or carcinomatous meningitis
• 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
• 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
• 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)
• 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.
• Prior organ or tissue allograft
• Further exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 4 centers

• Hokkaido Cancer Center — Hokkaido, Sapporo
• St. Marianna University Hospital — Kanagawa, Kawasaki
• Kansai Medical University Hospital — Osaka, Hirakata
• Shizuoka Cancer Center — Shizuoka, Sunto-gun

China · 3 centers

• The Affiliated Cancer Hospital, Guangxi Medical University — Nanning
• Shanghai Chest Hospital — Shanghai
• Shanghai Pulmonary Hospital — Shanghai

France · 3 centers

• CTR Leon Berard — Lyon
• HOP Timone — Marseille
• Institut Gustave Roussy — Villejuif

Spain · 3 centers

• Hospital Duran i Reynals — L'Hospitalet Del Llobregat
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Clinico De Valencia (INCLIVA) — Valencia

United Kingdom · 3 centers

• Leicester Royal Infirmary — Leicester
• Guy's Hospital — London
• Freeman Hospital — Newcastle upon Tyne

United States · 2 centers

• MedStar Georgetown University Hospital — Washington D.C.
• University of Kentucky Medical Center — Lexington

Belgium · 2 centers

• Universitair Ziekenhuis Antwerpen — Edegem
• Universitair Ziekenhuis Gent — Ghent

Germany · 2 centers

• Universitätsmedizin der Johannes Gutenberg-Universität Mainz — Mainz
• Robert Bosch Gesellschaft für medizinische Forschung mbH — Stuttgart

Poland · 2 centers

• Szpital Specjalistyczny W Brzozowie Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza — Brzozów
• Lower Silesian Oncology Centre — Wroclaw

Australia · 1 center

• Chris Obrien Lifehouse — Camperdown

Netherlands · 1 center

• Amsterdam UMC Locatie VUMC — Amsterdam

Identifiers

NCT: NCT07707895 · 1438-0036 · U1111-1334-0148 · 2026-525634-27

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗