Zocilurtatug Pelitecan Displays Meaningful Responses in Pretreated epNECs

Treatment with zocilurtatug pelitecan (ZL-1310) conferred clinically meaningful responses among patients with extrapulmonary neuroendocrine carcinomas (epNECs), according to findings from the open-label phase 1b/2 ZL-1310-002 trial (NCT06885281) presented at the 2026 American Association for Cancer Research Annual Meeting.¹

Specifically, among 34 patients treated with an intravenous solution of zocilurtatug pelitecan, the overall response rate (ORR) was 38.2%, with a disease control rate (DCR) of 55.9%. Moreover, the investigators observed target tumor reductions across multiple epNEC tumor types, and 1 patient previously treated with topotecan (Hycamtin) experienced a partial response. Cohort 1 (n = 18), which included exclusively those with gastroenteropancreatic (GEP) NECs, conferred an ORR of 33.3% and a DCR of 44.4%, and cohort 2, which included other NECs and DLL3-expressing solid tumors, conferred an ORR of 43.8% and a DCR of 68.8%.

“ZL-1310 demonstrated clinically meaningful responses in patients with previously treated epNECs, aggressive malignancies with limited treatment options,” Rohit Thummalapalli, MD, gastrointestinal medical oncologist at Memorial Sloan Kettering Cancer Center, wrote in the presentation with study coinvestigators.¹ “Responses were observed across epNEC tumors of different primary origins. Observed response rates appear favorable in the context of historical outcomes with chemotherapy in similar settings; cross-study comparisons should be interpreted with caution.”

The trial investigators 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. Additionally, patients with DLL3-expressing solid tumors were required to be relapsed/refractory to or have had a documented intolerance to standard-of-care therapy.

Across both cohorts, the median age was 56.0 years (range, 27-82), 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 (82.6%), 1 prior line of therapy (78.3%), and underwent prior platinum-based chemotherapy (95.7%).

The trial assessed tumor response by investigator assessment per RECIST v1.1 guidelines; patients with neuroendocrine prostate cancer were assessed per Prostate Working Group 3 (PCWG3) criteria as well. Additionally, DLL3 expression was assessed retrospectively per immunohistochemistry using H-score analysis.

Regarding safety, any-grade treatment-emergent adverse effects (TEAEs) occurred in 97.8% of patients across both cohorts, 30.4% of whom experienced grade 3 or higher TEAEs. The most common TEAEs included nausea (41.3%), anemia (37.0%), leukopenia (23.9%), and vomiting (23.9%). The most common grade 3 or higher TEAEs included anemia and neutropenia (both 6.5%).

Of note, 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 vs those who experienced disease progression.

“The [zocilurtatug pelitecan] data that we [presented] at AACR, alongside our ZL-6201 and ZL-1222 preclinical data, highlight the breadth, diversity and potential of our global oncology pipeline,” Rafael G. Amado, MD, president and head of Global Research and Development at Zai Lab, stated in a press release on the findings.² “The rapid progression of [zocilurtatug pelitecan] into pivotal development, with 3 registration-enabling studies planned by the end of this year, is a prime example of our strategy to deliver our first global oncology launch. This accelerated progress is made possible by our unique integrated US-China infrastructure, which allows us to evolve drug discovery into life-changing medicines with a focus on speed and quality."

References

1. Thummalapalli R, Lu M, Spira A, et al. Preliminary results from the phase 1b/2, open-label, multi-center study of ZL-1310, a DLL3-targeted ADC, in patients with neuroendocrine carcinomas and other selected solid tumors. Presented at: 2026 American Association for Cancer Research Annual Meeting. April 17-22, 2026; San Diego, CA. Abstract CT189.
2. Zai Lab presents new data demonstrating zocilurtatug pelitecan (zoci) induces rapid and robust intracranial responses in small cell lung cancer with brain metastases and promising activity in other neuroendocrine carcinomas. News release. April 17, 2026. Accessed April 24, 2026. https://tinyurl.com/ys2zek2k