Zocilurtatug pelitecan shows responses in pretreated extrapulmonary neuroendocrine carcinomas

Zocilurtatug pelitecan (ZL-1310) conferred clinically meaningful responses among patients with extrapulmonary neuroendocrine carcinomas in the open-label phase 1b/2 ZL-1310-002 trial. Among 34 patients treated with an intravenous solution of zocilurtatug pelitecan, the overall response rate was 38.2% and the disease control rate was 55.9%, with target tumor reductions across multiple epNEC tumor types.

The trial enrolled patients with advanced or metastatic epNEC following progression on or after platinum-based chemotherapy. Zocilurtatug pelitecan was administered intravenously at 1.6 mg/kg every 3 weeks in the absence of disease progression or unacceptable toxicity, and patients with DLL3-expressing solid tumors were required to be relapsed/refractory to or have had a documented intolerance to standard-of-care therapy.

Cohort 1, which included exclusively those with gastroenteropancreatic NECs, conferred an overall response rate of 33.3% and a disease control rate of 44.4%. Cohort 2, which included other NECs and DLL3-expressing solid tumors, conferred an overall response rate of 43.8% and a disease control rate of 68.8%. One patient previously treated with topotecan experienced a partial response.

Across both cohorts, the median age was 56.0 years, 65.2% were male, and 56.5% were Asian. The median Ki-67 index was 80.0, with 60.9% having an expression over 55%, and 76.1% had an ECOG performance status of 1. Most patients had stage IV disease at screening, 1 prior line of therapy, and prior platinum-based chemotherapy.

Tumor response was assessed by investigator assessment per RECIST v1.1 guidelines, and patients with neuroendocrine prostate cancer were assessed per Prostate Working Group 3 criteria. DLL3 expression was assessed retrospectively per immunohistochemistry using H-score analysis.

Regarding safety, any-grade treatment-emergent adverse effects occurred in 97.8% of patients across both cohorts, and 30.4% experienced grade 3 or higher treatment-emergent adverse effects. The most common treatment-emergent adverse effects included nausea, anemia, leukopenia, and vomiting, and the most common grade 3 or higher treatment-emergent adverse effects included anemia and neutropenia.

A preliminary analysis suggested no clear association between tumor response and DLL3 expression. A total of 28.6% of patients with an H-score of 0 observed a response, and patients with stable disease as best response had lower median DLL3 H-scores versus those who experienced disease progression.