A study in people with advanced extrapulmonary neuroendocrine cancer to compare obrixtamig plus carboplatin and etoposide treatment with standard chemotherapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH, Boehringer Ingelheim Espana S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-05-17

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2025-523869-22-00

WHO UTN

U1111-1328-6623

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others

The trial will compare obrixtamig in combination with carboplatin and etoposide vs. carboplatin and etoposide in patients with unresectable locally advanced or metastatic epNEC, previously untreated and tested positive. The primary objective is to demonstrate the superiority in overall survival (OS).

Secondary objectives 2

1. to demonstrate the superiority in progression-free survival (PFS) based on stratified log-rank test and hazard ratio.
2. patient-reported outcome (PRO) in mean change from baseline to Week 19 in the physical functioning domain using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)

Conditions and MedDRA coding

advanced or metastatic extrapulmonary neuroendocrine carcinoma

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed “Document Sharing Agreement”. Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined on the website. Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program. Access Criteria: For study documents – upon signing of a ‚Document Sharing Agreement‘. For study data – 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Patients with poorly differentiated unresectable locally advanced or metastatic epNEC with Ki-67 >20% or mitotic rate mitotic rate with number of mitoses >20 per 2 mm2, regardless of primary site (including site of unknown origin)
2. 2. Patients with tumours with mixed histologies are eligible only if neuroendocrine carcinoma component is predominant and represents more than 70% of the overall tumour tissue
3. 3. No prior systemic treatment for unresectable locally advanced or metastatic epNEC (except for the completed one cycle of standard platinum + etoposide). Prior peri-operative chemotherapy or -radiation for curative intention is allowed if at least 6 months have elapsed between completion of this therapy and diagnosis of unresectable locally advanced or metastatic disease
4. 4. Patients who have finished one cycle of standard platinum + etoposide regimen as first-line treatment (Cycle 0: etoposide with carboplatin or cisplatin, administered at a minimum dose of cisplatin 75 mg/m2 or carboplatin AUC 5 and etoposide 80 mg/m2) prior to randomisation
5. 5. Patients must comply with criteria for receiving further chemotherapy treatment as first-line SoC treatment within 28 days after the start of the initial chemotherapy (Cycle 0)
6. 6. Adequate archival FFPE tumour tissue, as specified in the Laboratory Manual, must be available for central laboratory analysis of DLL3 expression status. Tumours must be positive (as defined in the diagnostic study protocol) for DLL3 expression status assessed by investigational VENTANA DLL3 (SP347) RxDx Assay
7. 7. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
8. 8. 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)
9. Further inclusion criteria apply.

Exclusion criteria 9

1. 1. Presence of leptomeningeal disease and/or carcinomatous meningitis
2. 2. Patients with diagnosis of Merkel cell carcinoma or medullary thyroid carcinoma
3. 3. Patients with neuroendocrine prostate cancer
4. 4. Patients with well-differentiated neuroendocrine tumours of any grade according to the WHO classification, 5th edition
5. 5. Patients with a history of well differentiated NET tumour that transformed into poorly differentiated NEC
6. 6. Previous treatment with obrixtamig or other DLL3-targeting therapies (e.g. TcEs, cell therapies, antibody-drug conjugates, or radiopharmaceuticals)
7. 7. Previous treatment with anti-PD-1 or PD-L1 therapies during the one cycle of standard platinum + etoposide first-line chemotherapy (Cycle 0)
8. 8. Toxicity from previous treatments that has not resolved to ≤ CTCAE Grade 1 or grade prior to Cycle 0. Participants with alopecia any grade, CTCAE ≤Grade 2 asthenia/fatigue, amenorrhea/menstrual disorders any grade, CTCAE ≤Grade 2 peripheral neuropathy, and/or CTCAE ≤Grade 2 endocrinopathies controlled by replacement therapy, and toxicities, which are considered irreversible but stable for at least 4 weeks, per Investigator judgement may be eligible
9. Further exclusion criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS), defined as the time from randomisation until death from any cause

Secondary endpoints 9

1. PFS is defined as the time from randomisation until the earliest date of disease progression according to RECIST 1.1 based on investigator assessments or death from any cause, whichever occurs first
2. Change from baseline to Week 19 in the physical functioning domain of the EORTC QLQ-C30
3. Objective response (OR) is defined as a best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 (based on investigator assessments) from randomisation until the earliest date of disease progression, death, last evaluable tumour assessment before the start of next line of anti-cancer treatment, loss to follow-up, or withdrawal of consent
4. DoR, defined as the time from the first documented OR according to RECIST 1.1 until the earliest date of disease progression or death among patients with objective response based on investigator assessments
5. Disease control (DC), 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 1.1 based on investigator assessments from randomisation until the earliest of disease progression, death or last evaluable tumour assessment before start of next line of anti-cancer treatment, loss to follow-up or withdrawal of consent
6. Occurrence of treatment-emergent Grade 3 or greater CRS
7. Occurrence of treatment-emergent Grade 3 or greater ICANS
8. Occurrence of treatment-emergent AEs leading to permanent discontinuation of trial medication during the on-treatment period
9. Occurrence of treatment-emergent AEs leading to dose modification of trial medication (i.e. dose interruption, dose delay, dose reduction)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Third parties 1

Boehringer Ingelheim Espana S.A.

Sponsor organisation

Boehringer Ingelheim Espana S.A.

Address

Carrer Prat De La Riba 50, Sant Cugat Del Valles Sant Cugat Del Valles

City

Barcelona

Postcode

08174

Country

Spain

Sponsor responsibilities

Article 77 compliance

Boehringer Ingelheim International GmbH

Contact point sponsor

Boehringer Ingelheim International GmbH

Article 77 implementation

Boehringer Ingelheim International GmbH

Locations

14 EU/EEA countries · 71 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 199 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications