The US Food and Drug Administration (FDA) has granted Fast Track Designation to ZL-1310 for the treatment of extensive-stage small cell lung cancer (ES-SCLC). This decision underscores the ongoing need to develop new therapies for patients with small cell lung cancer (SCLC) and marks an important step forward in clinical progress.
The designation is based on updated results from an ongoing phase 1a/1b trial, which were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. The Fast Track Designation aims to expedite the development and review of drugs intended for the treatment or prevention of serious conditions that currently lack effective treatment options, allowing patients to access vital medications more quickly.
About ZL-1310
ZL-1310 is a next-generation Delta-like ligand 3 (DLL3)-targeted antibody-drug conjugate (ADC) developed by Zai Lab Limited. It is potentially the biopharmaceutical company’s first-in-class DLL3-targeted ADC to treat ES-SCLC and received Orphan Drug Designation from the FDA in January 2025.
DLL3 is an antigen that is often overexpressed in SCLC and other neuroendocrine tumors, and iits presence is commonly associated with poor clinical outcomes.1
ZL-1310 was developed as an anti-DLL3 monoclonal antibody linked to a topoisomerase 1 inhibitor.2 Its design incorporates a novel ADC technology platform, enabling it to influence the tumor microenvironment and overcome limitations commonly associated with first-generation ADCs.1
Trial Design
Enrolled participants in the global phase Ia/Ib trials received ZL-1310 as monotherapy or in combination with atezolizumab and carboplatin.2 Eligibility criteria included:
- Histologically or cytologically confirmed metastatic or extensive-stage SCLC
- At least one measurable target lesion, as defined by RECIST v1.1 on CT, PET/CT, or MRI
- Willingness to undergo a tumor biopsy or to provide an archived tumor tissue sample during screening
- Life expectancy is longer than 3 months3
The primary endpoints included the incidence of dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) across all three treatment arms.3
Key Findings and Safety Data
The objective response rate (ORR) among the 19 evaluable patients treated was 74%, with 14 patients achieving a partial response.4 The data regarding median duration of response (DOR) and progression-free survival (PFS) were not yet mature as of the data cut-off.4
TEAEs of any grade were reported in nearly all evaluable patients (96%), with 84% experiencing TEAEs related to ZL-1310.4 Less than half (40%) of the patients experienced grade 3 or higher TEAEs, with 20% specifically related to ZL-1310.4 Additionally, less than one-quarter (24%) of patients reported serious TEAEs.4
No TEAEs resulted in death or treatment discontinuation. However, TEAEs led to dose reductions in 20% of patients.4 These included:
- Grade 2 decreased appetite
- Grade 2 malaise
- Grade 3 hyponatremia
- Grade 2 vomiting
- Grade 4 neutrophil count decrease
- Grade 4 platelet count decrease4
Future Outlook
With high recurrence rates and limited effective therapies, SCLC remains one of the most challenging and aggressive forms of lung cancer.
The Fast Track Designation positions ZL-1310 for a potential accelerated approval in 2027, according to Zai Lab’s President and head of Global Research and Development, Rafael G. Amado, MD.
“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. Amado said in a recent press release.
Given its dual Orphan Drug and Fast Track designations, along with early efficacy and a manageable safety profile, ZL-1310 certainly shows signs of regulatory momentum and is poised to become a promising therapeutic option for SCLC.
References:
- 1. https://ir.zailaboratory.com/news-releases/news-release-details/zai-lab-receives-us-fda-fast-track-designation-zl-1310-dll3
- 2. https://www.cancernetwork.com/view/dll3-targeted-adc-produces-responses-in-previously-treated-es-sclc
- 3. https://clinicaltrials.gov/study/NCT06179069?cond=NCT06179069&rank=1
- 4. https://www.cancernetwork.com/view/zl-1310-receives-fda-fast-track-designation-for-extensive-stage-sclc?utm_source=chatgpt.com
