Zai Lab’s DLL3 ADC Zocilurtatug Pelitecan Receives FDA Orphan Drug Designation for Neuroendocrine Carcinomas

Zai Lab has received U.S. Food and Drug Administration Orphan Drug Designation for zocilurtatug pelitecan (zoci; formerly ZL-1310) for the treatment of neuroendocrine carcinomas (NECs), expanding the regulatory recognition of the investigational Delta-like ligand 3 (DLL3)-targeting antibody-drug conjugate (ADC). The designation highlights the urgent need for new therapies in NECs, where treatment options remain limited and patient outcomes are poor.

The latest designation builds on previous FDA Fast Track Designation for extra pulmonary neuroendocrine carcinomas (epNECs) and both Fast Track and Orphan Drug Designations for small cell lung cancer (SCLC). Zoci has also received Orphan Drug Designation from the European Medicines Agency (EMA) for pulmonary NECs, reinforcing its potential across multiple DLL3-positive neuroendocrine malignancies.

FDA Expands Regulatory Support for Zoci

The FDA grants Orphan Drug Designation to investigational therapies intended for rare diseases affecting fewer than 200,000 people in the United States. The status provides several development incentives, including eligibility for tax credits for qualified clinical trials, waiver of Prescription Drug User Fee Act (PDUFA) application fees, and potential seven-year market exclusivity if the therapy receives regulatory approval.

For Zai Lab, the latest designation strengthens regulatory support for zoci as development advances across multiple neuroendocrine cancer indications.

DLL3 Represents a Promising Therapeutic Target

Zocilurtatug pelitecan is an investigational DLL3-targeting antibody-drug conjugate. DLL3 is highly expressed in several aggressive neuroendocrine cancers, including small cell lung cancer and extra pulmonary neuroendocrine carcinomas, while showing minimal expression in normal tissues. Elevated DLL3 expression is generally associated with poor clinical outcomes, making it an attractive target for precision oncology.

Unlike conventional chemotherapy, ADCs deliver a cytotoxic payload directly to tumor cells expressing the target antigen, potentially improving antitumor activity while limiting exposure to healthy tissues.

Patients with previously treated NECs currently have no approved targeted therapies and few effective treatment options, highlighting a substantial unmet medical need.

Registration-Enabling Studies Planned Across Multiple Indications

Zai Lab is advancing zoci through an extensive late-stage clinical development program. The company plans to initiate three registration-enabling studies by the end of 2026, covering:

• Second- and third-line extensive-stage small cell lung cancer
• First-line small cell lung cancer
• Extrapulmonary neuroendocrine carcinomas

According to the company, emerging clinical data indicate encouraging systemic and intracranial antitumor activity alongside a potentially favorable safety profile. These findings support further evaluation of zoci both as monotherapy in previously treated disease and as part of first-line combination regimens with immune checkpoint inhibitors or T-cell engagers.

The company has not released efficacy or safety data associated with the current Orphan Drug Designation.

Executive Perspective

Rafael G. Amado, M.D., President and Head of Global Research and Development at Zai Lab, said the growing number of regulatory designations across major global agencies reflects the potential of zoci to become an important treatment option for patients with DLL3-expressing cancers. He added that the company remains focused on efficiently advancing its global clinical development program for the investigational ADC.

Future Development

The FDA’s latest Orphan Drug Designation adds further regulatory momentum to Zai Lab’s oncology pipeline as zocilurtatug pelitecan progresses toward pivotal clinical studies. With multiple expedited designations already secured in the United States and Europe, the DLL3-targeting ADC is positioned for several important development milestones over the coming months. Results from the planned registration-enabling trials will determine whether zoci can emerge as a new targeted treatment option for patients with aggressive neuroendocrine carcinomas, where therapeutic advances have remained limited for decades.

Reference

U.S. FDA Grants Orphan Drug Designation to Zai Lab’s DLL3-Targeting ADC Zocilurtatug Pelitecan (Zoci) for the Treatment of Neuroendocrine Carcinomas (NECs) – Zai Lab Limited