A Trial for the Treatment of Advanced Large-Cell Neuroendocrine Cancer of the Lung (ALPINE 2)

April 27, 2026 updated by: Technische Universität Dresden

A Phase II, Single-arm Trial on the Addition of the DLL3xCD3 Bispecific T-cell Engager Obrixtamig (BI 764532) to Standard-of-care Platinum-based First-line Treatment of Advanced Large-cell Neuroendocrine Carcinoma of the Lung

This phase II clinical trial evaluates the efficacy, safety and tolerability of Obrixtamig in addition to standard of care chemotherapy (Platinum/Etoposide) in LCNEC.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

75

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria: (main criteria)

  1. Patient has provided written informed consent and is able to consent
  2. Patients with pulmonary large-cell neuroendocrine carcinoma (LCNEC) defined by local histology and immunohistochemistry; patients with mixed histology are eligible if LCNEC is the predominant histology, i.e. ≥50%
  3. Patients with locally advanced or metastatic disease without curative treatment options
  4. All patients must have received one, but not more than one, cycle of platinum/etoposide chemotherapy with or without immune checkpoint inhibitor (standard-of-care; SoC). Other than that, patients must be previously untreated with systemic therapy.
  5. Measurable disease according to RECIST v1.11

Exclusion Criteria: (main criteria)

  1. Symptomatic brain metastases (Patients with asymptomatic brain metastases are allowed provided they are clinically stable, receiving no or a stable dose of anticonvulsants without steroid treatment for at least 3 weeks.)
  2. Known leptomeningeal disease
  3. Any prior systemic treatment for metastatic disease, except for one cycle of SoC as described under inclusion criteria
  4. Previous treatment with obrixtamig or any anti-DLL3 compound including T-cell engagers and antibody-drug conjugates

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Obrixtamig/Platinum/Etoposide
Obrixtamig/Platinum/Etoposide. Platinum will be carboplatin.
Drug: Obrixtamig
Obrixtamig (IMP) will be added to Platinum/Etoposide (Standard-of-Care). Three cycles of combined immunochemotherapy 3qw will be followed by maintenance with obrixtamig monotherapy until progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: app. 69 months
To assess the efficacy of Obrixtamig in addition to standard of care chemotherapy (Platinum/Etoposide) in LCNEC as measured by overall survival.
app. 69 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: app. 69 months
defined as PR or CR according to RECIST v1.1 as assessed by local investigator
app. 69 months
Progression-Free Survival (PFS)
Time Frame: app. 69 months
defined as time from first application of obrixtamig to progression according to RECIST v1.1, or to start of any other anticancer treatment, or death from any cause whichever occurs first
app. 69 months
Duration Of Response (DOR)
Time Frame: app. 69 months
defined as time from first documented PR or CR according to RECIST v1.1 to time of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first
app. 69 months
Disease Control Rate (DCR)
Time Frame: app. 69 months
defined as combination of CR, PR and SD according to RECIST v1.1
app. 69 months
immune Objective Response Rate (iORR)
Time Frame: app. 69 months
immune ORR (iORR) defined as iPR or iCR according to iRECIST
app. 69 months
immune Progression Free Survival (iPFS)
Time Frame: appr. 69 months
defined as time from first application of obrixtamig to progression according to iRECIST, clinical progression with change of treatment or death from any cause, whichever occurs first
appr. 69 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS, OS, DOR and ORR in central pathology confirmed cases of LCNEC
Time Frame: app. 69 months
app. 69 months
PFS, OS, DOR and ORR in defined LCNEC molecular subtypes
Time Frame: appr. 69 months
(type I, type II - NSCLC and SCLC like) and depending on DLL3 expression to identify potential correlation between responses in molecular subtypes and DLL3 expression levels (high vs. low)
appr. 69 months
Quality of Life assessment
Time Frame: appr. 69 months
Changes from baseline in EORTC-QLQ-C30 as well as QLQ-LC13 global and LC specific health/QoL score.
appr. 69 months
further exploratory end points
Time Frame: appr. 69 months

For other exploratory end points respective biomaterials will be banked within the trial but analyses will be contingent on specimen availability. These analyses will include but are not limited to:

  • Changes in cellular and humoral immune effectors in peripheral blood and their correlation with response
  • Mutational landscape of LCNEC in comparison to SCLC as well as squamous and adenocarcinoma of the lung
  • Dynamics of circulating tumor DNA levels (changes from baseline)
  • Mechanisms of therapy resistance (changes of immune invasion and mutational landscape in tumor re-biopsy upon progression)
  • Expression of DLL3 in pre- and post-treatment samples including analyses in BI-designated central lab
  • Composition of the tumor microenvironment using multiplex immunofluorescence
appr. 69 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Technische Universität Dresden

Investigators

  • Principal Investigator: Martin Wermke, Prof. Dr. med., Technische Universität Dresden, Medizinische Fakultät

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

April 1, 2032

Study Completion (Estimated)

April 1, 2032

Study Registration Dates

First Submitted

April 15, 2026

First Submitted That Met QC Criteria

April 27, 2026

First Posted (Actual)

May 1, 2026

Study Record Updates

Last Update Posted (Actual)

May 1, 2026

Last Update Submitted That Met QC Criteria

April 27, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TUD-ALPIN2-089
  • 2025-524345-28-00 (Ctis)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Large Cell Neuroendocrine Carcinoma of the Lung

Clinical Trials on Obrixtamig

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bosnia & Herzegovina

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe