A randomized, open-label, phase 3 study of ZL-1310, a DLL3 antibody-drug conjugate (ADC), compared to investigator’s choice therapy in participants with relapsed small cell lung cancer (DLLEVATE).

TPS8136 Background: Small Cell Lung Cancer (SCLC) is a neuroendocrine tumor with high proliferation rate, early metastasis and poor prognosis. DLL3 is a validated target for neuroendocrine tumor and is highly expressed in SCLC. ZL-1310 is a novel antibody-drug conjugate (ADC) that employs the TMALIN (Tumor Microenvironment Activable LINker-payload) platform, an anti-DLL3 monoclonal antibody linked to a topoisomerase I inhibitor payload via a protease-cleavable linker. ZL-1310 has demonstrated encouraging systemic efficacy in heavily pre-treated ES-SCLC and showed intracranial activities. Methods: DLLEVATE is a randomized, open-label phase III study to further evaluate the efficacy and safety of ZL-1310 compared to investigator's choice of locally approved and available single agent therapy (ICT). This multi-country Phase III study (NCT07218146) enrolls adults with Extensive Stage (ES)-SCLC patients (pts) who have progressed after platinum-based first-line (1L) therapy or after tarlatamab as second-line (2L) therapy. Those with stable or asymptomatic BM are eligible (including those with no prior brain radiotherapy). The eligible pts are randomized at 1:1 according to presence/absence of brain metastasis, sensitivity to prior chemotherapy and with/without prior tarlatamab. ZL-1310 is given intravenously every 3 weeks until disease progression or unacceptable toxicity. Systemic efficacy is assessed by investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Intracranial efficacy is assessed by blind independent radiologists using Modified Criteria for Radiographic Response Assessment in Neuro-Oncology (mRANO). The study has one interim analysis based on Objective Response Rate (ORR) assessed by Blind Independent Review Committee (BIRC) and the primary analysis based on Overall Survival (OS). Enrollment is underway, and is planned at ~250 sites across several continents. Clinical trial information: NCT07218146 .