EPISODE 48 - NEN TREATMENTS: FOCUS ON DLL3

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ABOUT THIS EPISODE

DLL3 is emerging as a promising new target for neuroendocrine cancers. In this episode, Dr. Rohit Thummalapalli, medical oncologist at Memorial Sloan Kettering Cancer Center, explains what DLL3 is, how it works, who might benefit, and what current clinical trials are teaching us. He breaks down the science, treatment options, and future directions in a way that is clear, approachable, and designed to help patients and families better understand this developing area of care.

MEET DR. ROHIT THUMMALAPALLI

Rohit Thummalapalli is a gastrointestinal medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center specializing in clinical care and research in patients with neuroendocrine and biliary tract cancers. Originally from Florida, Dr. Thummalapalli completed medical training at Harvard and Johns Hopkins before arriving at MSK as a medical oncology fellow in 2021, and started on faculty in 2024.

TOP TEN QUESTIONS:

Understanding the Basics

1. What is immunotherapy? How does immunotherapy work?

2. What is DLL3? How does it work in the context of neuroendocrine cancer?

3. How is DLL-targeted therapy similar to or different from other types of immunotherapy? Is there evidence that one works better than another?

Indications, Use, Access & Availability

4. When is DLL3 used in neuroendocrine cancers? 

   1. What types of neuroendocrine cancer might express DLL3?

   2. How does someone know if this is a potential treatment option for them?

c. At what point in a patient’s treatment journey might DLL3 be considered?

d. How and where DLL3 is available for neuroendocrine cancer patients? What are other ways, if any, to access DLL3?

Testing for DLL3 Expression

5. How does someone find out if their tumors express DLL3 receptors? 

   1. How & where is DLL3 expression tested? It it tested through tissue samples, imaging, or something else?

   2. Is there a minimal level of DLL3 expression that is required to receive the treatment? (Does the threshold vary by trial?)

   3. Does the level of DLL3 expression differ by institution? 

   4. Does the level of DLL3 expression predict how well someone might respond to treatment?

   5. Can the tumor expression of DLL3 vary from tumor to tumor? Can it vary over time, meaning can tumors gain or lose expression?

   6. Do you measure the DLL3 expression following treatment?

Treatment Considerations

6. How effective is DLL3-targeted therapy in neuroendocrine cancers? What is the goal of treatment with DLL3 – shrinkage, stabilization, symptom relief? How long is it expected to work? How do you measure the response to DLL3 treatment? 

7. Can DLL3 be combined with other therapies? 

Decision-Making and Patient Counseling

8. How do you decide when to offer DLL3 for someone with neuroendocrine cancer? 

   1. What factors or prior treatments might make someone ineligible for DLL3 therapy?

   2. Could receiving DLL3 exclude a patient from other treatments or clinical trials?

9. How do you counsel patients who are considering DLL3? 

   1.  What should they know about how the treatment is given, possible side effects, and what’s known (or unknown) about long-term safety?

   2. What should one expect in terms of frequency of visits, hospitalization and side effects?

   3. Can someone still work while receiving DLL3?

Looking Ahead

10. What are the key questions you hope to answer about DLL3 in the next year? What do you hope to learn over the next 3 to 5 years?

RESOURCES

LISTEN

Neuroendocrine Cancer Foundation Podcast Episode 36: NEN Treatments: Focus on Immunotherapy

EXPLORE

Clinical Trials Guide: Immunotherapy 

READ

Landscape of functional DLL3 expression in gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) (May 28, 2025)

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 (May 28, 2025)

Delta-Like Ligand 3 Expression and Functional Imaging in Gastroenteropancreatic Neuroendocrine Neoplasms - JCO Precision Oncology, November 20, 2025

WATCH

Dr. Strosberg on Research Clarifying the Role of Obrixtamig in SCLC and Other Neuroendocrine Cancers (May 5, 2025)

Obrixtamig Could Broaden the Reach of DLL3/CD3-Targeted BiTEs in Small Cell Lung and Other Neuroendocrine Cancers (May 5, 2025)

NOVEL NON-IMMUNOTHERAPY-BASED DLL3-TARGETED CLINICAL TRIALS

Immuno-PET Imaging of Neuroendocrine Tumors Using 89Zr-DFO-SC16.56, a DLL3-targeting Monoclonal Antibody 

A Study of ZL-1310 in Participants With Selected Solid Tumors

225Ac-ABD147 to Establish Optimal Dose in Patients With SCLC and LCNEC of the Lung That Previously Received Platinum-based Chemotherapy

DISCLAIMER

The Neuroendocrine Cancer Foundation Podcasts are created for educational purposes only and do not substitute for medical advice. The views shared in this Podcast are the personal opinions of the experts and do not necessarily reflect the views of the Neuroendocrine Cancer Foundation. Please contact your medical team with questions or concerns about your individual care or treatment.

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