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

ClinicalTrials.gov ID

NCT07707895

Lead Sponsor

Boehringer IngelheimINDUSTRY

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Phase 1Phase 2

Enrollment

60Estimated

Last Update Posted

Sep 2, 2026Actual

Start Date

Sep 29, 2026Estimated

Primary Completion Date

Apr 26, 2030Estimated

Completion Date

Apr 26, 2030Estimated

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

Brief 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.

• Small Cell Lung Cancer
• Large Cell Neuroendocrine Lung Carcinoma
• Extrapulmonary Neuroendocrine Carcinoma of Small Cell Histology
• Extrapulmonary Neuroendocrine Carcinoma of Large Cell Histology

• Obrixtamig
• ZL-1310
• Atezolizumab

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

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 Purpose

Treatment

Allocation

Non-Randomized

Interventional Model

Sequential Assignment

Masking

None (Open Label)

Lead Sponsor

Boehringer IngelheimINDUSTRY

Collaborators

Zai LabUNKNOWN

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