FDA Grants Fast Track Designation to ZL-1310 in Small Cell Lung Cancer

The FDA granted fast track designation to Zai Lab's ZL-1310 for extensive-stage small cell lung cancer after early data showed tumor shrinkage.

The United States Food and Drug Administration (FDA) has granted fast track designation to ZL-1310 for the treatment of extensive-stage small cell lung cancer, according to a news release from Zai Lab.

Fast track designation helps speed the development and review of drugs for serious conditions or unmet medical needs, as per the release.

Interim data from part 1a of a phase 1 trial showed early signs of antitumor activity with ZL-1310, according to findings presented at the EORTC-NCI-AACR Symposium in October 2024.

Among 25 patients treated across four dose levels, 19 of those received at least one follow-up scan. Of those, 74% saw their tumors shrink or disappear after treatment. Responses were seen in patients with DLL3 H-scores as low as 5, though no response occurred in the patient whose tumor did not express DLL3.

ZL-1310 is a potential first-in-class Delta-like ligand (DLL3) antibody-drug conjugate (ADC).

“The FDA’s decision to grant fast track designation to ZL-1310 highlights the significant need for expanded treatment options for patients with SCLC and represents an important step in our efforts to advance a novel therapeutic option as quickly as possible,” Dr. Rafael G. Amado, president, head of global research and development, Zai Lab, said in the news release. “This designation reinforces the clinical progress we have achieved for ZL-1310 to-date, and we remain on track to initiate a pivotal study in small cell lung cancer later this year, positioning us for a potential accelerated approval in 2027.”

Regarding safety, in a group of 25 patients, ZL-1310 was generally well tolerated, with most side effects being mild or moderate. One patient experienced a dose-limiting case of temporary but severe low blood counts at the highest tested dose. Serious treatment-related side effects occurred in 2 patients, and 3 needed dose reductions. No one stopped treatment due to side effects.

Currently, ZL-1310 is being evaluated in an ongoing global phase 1a/1b clinical trial and previously received an orphan drug designation for small cell lung cancer from the FDA. Study data will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, where Zai Lab will highlight updated data and outline the next steps in clinical development.

What is Small Cell Lung Cancer and DLL3?

Small cell lung cancer (SCLC) is a fast-growing, aggressive disease that makes up about 15% of the 2.5 million global lung cancer diagnoses each year, according to the release. Roughly two-thirds of patients are diagnosed at an extensive stage, when the cancer has already spread.

SCLC and other neuroendocrine tumors often overexpress DLL3, a protein linked to poor outcomes. ZL-1310 is an investigational treatment designed to target DLL3. It combines a humanized anti-DLL3 antibody with a novel topoisomerase 1 inhibitor using a cleavable linker. This antibody-drug conjugate was developed using the TMALIN platform, which is intended to address some limitations of earlier ADC therapies by working with the tumor microenvironment.

More About the Phase 1a/1b Clinical Trial

This early-phase, open-label study is testing the safety, tolerability and pharmacokinetics of ZL-1310 alone or in combination with Tecentriq (atezolizumab) — with or without carboplatin — in patients with extensive-stage small cell lung cancer. The trial uses ascending, multiple doses to help determine how the drug behaves in the body and whether it can be safely combined with other treatments.

In the early phase of this study, patients are receiving ZL-1310 alone or with Tecentriq to find a safe dose. In the expansion phase, patients are being treated with ZL-1310 at two dose levels or in combination with Tecentriq and carboplatin as induction therapy, followed by ZL-1310 and Tecentriq for maintenance.

Researchers are primarily evaluating how often patients experience serious or dose-limiting side effects. Secondary goals include measuring response rates, how long responses last, time without disease worsening, overall survival, disease control, and how the drug behaves in the body.

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