ZL-1310 Receives FDA Fast Track Designation for Extensive-Stage SCLC

ZL-1310 was previously granted orphan drug designation by the FDA in January 2025.

The FDA has granted fast track designation to ZL-1310 as a treatment for patients with extensive-stage small cell lung cancer (ES-SCLC), according to a news release from the drug’s developer, Zai Lab Limited.¹

Of note, ZL-1310 was previously granted orphan drug designation by the FDA in January 2025.² Furthermore, updated results from an ongoing phase 1a/1b trial (NCT06179069) assessing the agent in ES-SCLC will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Preliminary results from the trial were previously presented at the EORTC-NCI-AACR (ENA) Symposium 2024 in October 2024.³

“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,” Rafael G. Amado, MD, president and head of Global Research and Development at Zai Lab, said in the news release.¹ “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 [SCLC] later this year, positioning us for a potential accelerated approval in 2027.”

Among 19 patients treated on the phase 1a/1b trial who were evaluable for preliminary efficacy, the objective response rate (ORR) was 74% (n = 14; 95% CI, 48.8%-90.9%) and composed of 14 (74%) partial responses (PRs). Additionally, 3 (16%) patients had stable disease, and 2 (10%) experienced disease progression. The median time to response was 1.38 months (range, 1.2-2.8), with 6 response evaluable patients with brain metastases achieving a PR. All patients at the 1.6 mg/kg (n = 6) and 2.0 mg/kg (n = 1) dose levels achieved a PR.

At a median follow-up of 2.4 months (range, 0.3-6.5), the median duration of response (DOR) and progression-free survival (PFS) data were not mature as of data cut-off. Additionally, at data cut-off, 13 of 14 responders remained on study treatment, including 2 of 3 in the 0.8 mg/kg cohort, all 6 in the 1.6 mg/kg cohort, 1 in the 2.0 mg/kg cohort, and all 4 in the 2.4 mg/kg cohort.

Patients in the phase 1a/1b trial were assigned to receive ZL-1310 as monotherapy, as a combination with atezolizumab (Tecentriq), or in combination with atezolizumab and carboplatin.⁴ The coprimary end points of the study were the dose-limiting toxicities (DLTs) and adverse effects (AEs) of the 3 treatment arms. Secondary end points included ORR per RECIST v 1.1 criteria, DOR, PFS, disease control rate, and overall survival.

Safety data presented at ENA revealed that among evaluable patients treated with ZL-1310 (n = 25), any-grade treatment-emergent AEs (TEAEs) were reported in 24 (96.0%) patients, of whom 21 (84.0%) experienced TEAEs related to ZL-1310. Additionally, 10 (40%) patients experienced grade 3 or greater TEAEs, including 5 (20.0%) directly related to ZL-1310. Serious TEAEs were reported in 6 (24.0%) patients, including 2 (8.0%) experiencing serious TEAEs related to ZL-1310.

Additional data revealed that TEAEs leading to dose interruption occurred in 5 (20.0%) patients, TEAEs leading to dose reduction occurred in 3 (12.0%), and no TEAEs led to drug discontinuation. TEAEs leading to dose reduction included single instances of grade 2 decreased appetite, grade 2 malaise, grade 3 hyponatremia, grade 2 vomiting, grade 4 neutrophil count decrease, and grade 4 platelet count decrease.

No TEAEs led to death, and 1 DLT event were reported. The transient DLT event occurred in the 2.4 mg/kg cohort and consisted of grade 4 instances of neutropenia and thrombocytopenia.

References

1. Zai Lab receives U.S. FDA fast track designation for ZL-1310, a DLL3-targeted antibody-drug conjugate, for treatment of extensive-stage small cell lung cancer. News release. Zai Lab Limited. May 19, 2025. Accessed May 20, 2025. https://tinyurl.com/2yccrfv4
2. 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). News release. Zai Lab Limited. January 22, 2025. Accessed May 20, 2025. https://tinyurl.com/yc4tehn5
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 - NCT06179069. EJC. 2024;211(suppl 1):114534. doi:10.1016/j.ejca.2024.114534
4. A study of ZL-1310 in subjects with small cell lung cancer. ClinicalTrials.gov. Updated January 10, 2025. Accessed May 20, 2025. https://tinyurl.com/3ey25prv