FDA Grants Orphan Drug Designation to ZL-1310 for Treatment of Small Cell Lung Cancer

The FDA granted orphan drug designation (ODD) to Zai Lab Limited’s ZL-1310, a highly active, first-in-class, delta-like ligand 3 (DLL3) antibody-drug conjugate (ADC) for the treatment of patients with small cell lung cancer (SCLC), according to a news release from Zai Lab.¹

Small cell lung cancer is an aggressive disease that can spread throughout the body. | Image Credit: © Best | stock.adobe.com

DLL3 is an antigen over-expressed in a multitude of neuroendocrine tumors and is often associated with poor clinical outcomes, considered by experts as a validated therapeutic target for patients with SCLC. ZL-1310 targets DLL3 through deploying a humanized, anti-DLL3 monoclonal antibody linked to a novel camptothecin derivative as its payload. ZL-1310 was designed with novel technology that can leverage the tumor microenvironment to defeat obstacles typically associated with first-generation ADC therapies.¹

“These patients have an urgent need for innovative treatment options with improved efficacy, safety and ready access in tertiary care and community settings,” Rafael G Amado, MD, president and head of global research and development at Zai Lab, said in the news release. “ZL-1310 has demonstrated promising objective response rates and a favorable safety profile from the ongoing Phase 1 trial in patients with recurrent SCLC recently disclosed.”¹

Amado continued, writing that “We look forward to continuing to advance the clinical development of this promising asset across lines of therapy in SCLC and other DLL3-expressing tumors.”¹

ZL-1310 is being further studied in an ongoing phase 1a/1b clinical trial evaluating the drug as a monotherapy and in combination with atezolizumab (Tecentriq; Genetech Inc), a monoclonal antibody designed to bind with PD-(L)1 proteins and block interactions with PD-1 and B7.1 receptors, for treatment in patients with extensive stage-SCLC (ES-SCLC).^1,2

Preliminary data from this trial of patients with previously treated ES-SCLC following treatment with at least 1 prior platinum-based chemotherapy regimen was presented at the EORTC-NCI-AACR (ENA) Symposium 2024. These results indicated that ZL-1310 has a favorable pharmacokinetic and safety profile, including indications of early clinical activity observed at the first dose level.^1,3

A total of 7 patients with ES-SCLC were treated in 2 dose escalation cohorts and received at least 1 dose of ZL-1310. Importantly, there were no dose-limiting toxicities, treatment-related adverse events (AEs) of grade 3 or higher, or specific instances of neutropenia, neuropathy, or ocular toxicity were observed to date. In 3 of the 4 response-evaluable subjects, partial responses were observed, including a subject achieving a near-complete resolution of an asymptomatic brain metastasis.³

As investigations of ZL-1310 and other treatments for SCLC continue and new drugs enter development, pharmacists and treatment providers should be aware of new clinical trial results and be prepared to counsel patients who can benefit the most from these treatments. ES-SCLC is an aggressive and common form of cancer and is associated with high rates of relapse and a poor prognosis, necessitating that a patient care team optimize disease management with new and effective treatments.^1,3

REFERENCES

1. Zai Lab Limited. Zai Lab receives orphan drug designation from the U.S. FDA for ZL-1310 (DLL3 ADC) for the treatment of small cell lung cancer (SCLC). BusinessWire. News Release. Released January 22, 2025. Accessed January 23, 2025. https://www.businesswire.com/news/home/20250123670143/en/Zai-Lab-Receives-Orphan-Drug-Designation-from-the-U.S.-FDA-for-ZL-1310-DLL3-ADC-for-the-Treatment-of-Small-Cell-Lung-Cancer-SCLC

2. Halpern L. Atezolizumab and hyaluronidase-tqjs subcutaneous formulation receives FDA approval to treat multiple forms of cancer. Pharmacy Times. Published September 13, 2024. Accessed January 23, 2025. https://www.pharmacytimes.com/view/atezolizumab-and-hyaluronidase-tqjs-subcutaneous-formulation-receives-fda-approval-to-treat-multiple-forms-of-cancer

3. Spira A, Dowlati A, Zhao J, et al. Preliminary results from a phase Ia/Ib, open-label, multicenter study of ZL-1310, a DLL3-targeted ADC, to evaluate the safety, tolerability, and pharmacokinetics in subjects with small cell lung cancer. Euro Journ Cancer. 2024;114534:211S1. doi:10.1016/j.ejca.2024.114534