Zai Lab’s DLL3 ADC Zoci secures EMA orphan designation for SCLC

Edited by Robert McTiernan··4 min read

Zai Lab’s zocilurtatug pelitecan has secured EMA Orphan Drug Designation (ODD) for pulmonary neuroendocrine carcinomas (NECs), a category dominated by small cell lung cancer (SCLC), as the company advances toward three registration-enabling studies planned by year-end. Zai Lab Limited (Nasdaq: ZLAB; HKEX: 9688), headquartered in Shanghai and Cambridge, Massachusetts, announced the designation for zocilurtatug pelitecan (Zoci, formerly ZL-1310), its Delta-like ligand 3 (DLL3)-targeting antibody-drug conjugate (ADC), on June 16, 2026. The EMA’s Committee for Orphan Medicinal Products (COMP) concluded that preliminary clinical data in patients with relapsed or refractory extensive-stage SCLC suggest zoci may offer a more favorable effect than currently authorized therapies, including durable responses — a finding the COMP characterized as a clinically relevant advantage.

The EMA ODD for pulmonary neuroendocrine carcinoma follows a sequence of US FDA designations for the same molecule: Fast Track Designation (FTD) and Orphan Drug Designation (ODD) for SCLC, and a more recently granted FTD for extrapulmonary neuroendocrine carcinomas (epNECs). The EMA designation provides potential market exclusivity following approval, reduced development fees, and enhanced regulatory support — incentives that are materially relevant for a company positioning zoci as its first global oncology launch.

Zoci targets DLL3, a Notch pathway ligand overexpressed on the surface of the majority of SCLC tumors and a substantial fraction of extrapulmonary NECs, with minimal expression on normal adult tissue. The ADC delivers a camptothecin-based topoisomerase I inhibitor payload via a cleavable linker, exploiting DLL3 surface expression to direct cytotoxic activity to neuroendocrine tumor cells.

Clinical data package

The COMP’s determination rested on preliminary clinical data; the most detailed public readout comes from the AACR Annual Meeting in April 2026, which Zai Lab cited as the basis for the EMA submission. Two datasets were presented.

In a Phase I study (NCT06179069) evaluating zoci in previously treated extensive-stage SCLC patients with baseline brain metastases, the intracranial objective response rate (ORR) across all doses was 54%, rising to 62% at the 1.6 mg/kg dose level. The intracranial complete response rate was 17%, with a median time on intracranial response of approximately nine months. These figures are notable in a patient population for which no drug carries an approved label specifically for intracranial disease.

In a separate Phase Ib study (ZL-1310-002) evaluating zoci at 1.6 mg/kg intravenously every three weeks in previously treated epNEC patients, with a data cutoff of February 18, 2026 and median follow-up of 3.7 months, the ORR in 34 response-evaluable patients was 38.2% (13 of 34), with a disease control rate of 55.9%. These datasets collectively informed the COMP’s characterization of durable responses constituting a clinically relevant advantage over currently authorized therapies in relapsed or refractory extensive-stage SCLC — the most prevalent pulmonary NEC subtype.

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SCLC accounts for approximately 15% of the estimated 2.5 million lung cancer diagnoses annually, translating to roughly 375,000 new cases per year worldwide. It is among the most aggressive solid tumors, with limited approved second-line options after platinum-based chemotherapy plus checkpoint inhibitor combinations.

Research context

The DLL3-targeting landscape has become one of the more active areas in thoracic oncology. Amgen’s tarlatamab (IMDELLTRA), a DLL3 × CD3 bispecific T-cell engager, received US FDA approval in May 2024 for previously treated extensive-stage SCLC and represents the current benchmark, with an ORR of approximately 40% and median duration of response of roughly 9.7 months in the DeLLphi-301 Phase II trial. Boehringer Ingelheim’s obrixtamig (BI 764532), another DLL3/CD3 T-cell engager, is advancing into a Phase III trial and has entered a clinical collaboration with Zai Lab to evaluate obrixtamig combined with zoci in SCLC and other NECs. That combination study reflects a broader strategic bet that DLL3-directed T-cell redirection and DLL3-targeted ADC payloads may be mechanistically complementary.

Zoci’s differentiation rests partly on its intracranial activity data and its safety profile, which Zai Lab describes as supporting use as a backbone ADC in combination regimens, including with checkpoint inhibitors and T-cell engagers. The EMA ODD for pulmonary NEC, combined with the recently granted FDA FTD for epNECs, provides Zai Lab with orphan incentives across both major NEC subtypes in the two largest regulatory jurisdictions.

Zai Lab has indicated plans to initiate three registration-enabling studies — in second- and third-line SCLC, first-line SCLC, and epNECs — by the end of 2026, with the zocilurtatug orphan drug designation in the EU and the accumulated FDA designations providing the regulatory foundation for those programs across major markets.

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