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A novel antibody-drug conjugate, zocilurtatug pelitecan, is showing real promise for patients with extrapulmonary neuroendocrine carcinomas (EP-NECs) — a rare, aggressive cancer with grim outcomes after first-line therapy. In a phase 1b/2 trial, the drug achieved a 40% objective response rate in heavily pretreated patients, with a median duration of response of 5.6 months. A phase 3 trial is now in the works.
Extrapulmonary neuroendocrine carcinomas (EP-NECs) are aggressive cancers with no established standard of care after first-line platinum-based chemotherapy fails — and median overall survival in that setting is typically under 6 months. A new antibody-drug conjugate (ADC), zocilurtatug pelitecan, is offering a potential lifeline. The drug targets DLL3, a protein overexpressed in neuroendocrine carcinomas, and received FDA orphan drug designation in August 2026.
Data from an open-label, multicenter phase 1b/2 trial (NCT06885281), presented at the 2026 NANETS Multidisciplinary NET Medical Symposium, showed that the drug produced durable responses even in heavily pretreated patients — including some with low or absent DLL3 expression. Some patients achieved complete responses lasting close to a year. The safety profile was manageable, with no grade 3+ interstitial lung disease events and only one treatment-related discontinuation.
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Why it matters: EP-NECs are a rare but deadly cancer with virtually no good options after first-line treatment. A 40% response rate in this setting is clinically significant, and a planned phase 3 trial could pave the way for the first approved second-line therapy for these patients.
