Presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting* by Jaume Capdevila, a Medical Oncologist of the Vall d’Hebron University Hospital and Senior Investigator of VHIO’s Upper Gastrointestinal and Endocrine Tumors Group, initial results from an ongoing first-In-human phase I, non-randomized, open-label clinical trial point to the promise of novel targeted immunotherapy obrixtamig in patients with extrapulmonary neuroendocrine carcinomas (EPNECs).
EPNECs constitute a rare group of highly aggressive neuroendocrine tumors that arise from neuroendocrine cells, which are specialized cells of the neuroendocrine system with both hormonal and neuronal functions. These cancers can occur in any organ type except lung, unlike small cell neuroendocrine carcinoma (SCNC) which is a more frequent type of neuroendocrine carcinoma that most commonly develops in the lungs.
“Extrapulmonary neuroendocrine carcinomas are a heterogeneous and poorly differentiated group of aggressive cancers associated with a poor prognosis and limited treatment options. Chemotherapy is the current standard of care in both the first-line and relapsed or refractory settings. The median overall survival is less than one year, underscoring the need for novel, effective therapies to improve patient outcomes,” said Jaume Capdevila, Principal Investigator of this multi-center study.
80% of EPNEC tumors express DLL3
The DLL3 protein is essential for embryonic development and cell differentiation, but is either not expressed or found at very low levels in most adult tissues. However, in some tumor types DLL3 is abnormally expressed on the surface of cancer cells and is implicated in tumor proliferation. DLL3 can be found on the surface of 80% of EPNEC tumors, making it a potential target for new therapies.
Bispecific T-cell engagers (BiTE) are a type of immunotherapy engineered to redirect the immune system’s T cells to recognize and kill cancer cells. Obrixtamig is an investigational bispecific antibody that is being evaluated for the treatment of certain cancers, particularly those expressing DLL3.
This present phase 1 study, conducted at 11 different sites including VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – CaxiaResearch, was designed to assess the efficacy and safety of obrixtamig in patients with advanced DLL3-positive tumors, including EPNEC with high or low DLL3 expression levels, for whom previous treatment was not successful.
“This ongoing study included sixty patients, half with tumors categorized as DLL3-high, expression and the other half as DLL3-low. Initial results show that patients with DLL3-high tumors had a higher overall response rate and disease control rate than those with DLL3-low tumors, and that obrixtamig had a manageable safety profile in patients, regardless of DLL3 expression,” added Capdevila.
Findings show that the disease control rate was 67% in the DLL3-high group versus 27% in those patients whose tumors were categorized as DLL3-low. The objective response rate was 40% in patients with high DLL3 expression compared to 3% in patients with low levels of the protein.
“These preliminary results show that obrixtamig has promising antitumor activity, especially in patients with tumors with high DLL3 expression, and support further investigations of this novel targeted immunotherapy in this patient population,” he concluded.
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Reference
*2025 ASCO Annual Meeting, May 30 – June 3, Chicago ILASCO 2025
Corresponding session details:
Oral Abstract Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Date: May 30, 2025
Time: 14:45h CT, 21:45h CEST
Room: Hall D1
Chairs: Jason Timothy Henry, MD, Sarah Cannon Research Institute at HealthONE, and Timothy A. Yap, MD, PhD, The University of Texas MD Anderson Cancer Center.
- Efficacy and safety of the DLL3/CD3 T-cell engager obrixtamig in patients with extrapulmonary neuroendocrine carcinomas with high or low DLL3 expression: Results from an ongoing phase I trial. Jaume Capdevila, Valentina Gambardella, Yasutoshi Kuboki, Olatunji B. Alese, Daniel Morgensztern, Cyrus Sayehli, Miguel F. Sanmamed, Edurne Arriola, Matus Studeny, Mohamed Bouzaggou, Zhiheng Chen, Valeria Lifke, Juergen Wolf, Martin Wermke.
