The DLL3-targeting antibody-drug conjugate zocilurtatug pelitecan received FDA orphan drug designation for the management of neuroendocrine carcinomas.
The FDA has granted orphan drug designation to zocilurtatug pelitecan (formerly ZL-1310), a DLL3-targeting antibody-drug conjugate (ADC), for the treatment of patients with neuroendocrine carcinomas (NECs).¹
NECs are aggressive malignancies that frequently express DLL3, and no targeted therapies, and no approved standard of care exist for previously treated patients with NECs.
“[Zocilurtatug pelitecan] has now received important regulatory designations around the world, signifying its potential to become an important new therapeutic option for patients with multiple types of cancer with DLL3 expressions,” Rafael G. Amado, MD, president and head of global research and development at Zai Lab, stated in a news release. “Given the need among the NEC patient community, we are focused on efficiently advancing our clinical programs for this investigational DLL3-targeting ADC.”
The FDA previously granted fast track designation to zocilurtatug pelitecan for the treatment of patients with extrapulmonary NECs (epNECs), as well as both
Zocilurtatug Pelitecan Regulatory Designations in NECs
Zocilurtatug pelitecan targets DLL3, which is a validated therapeutic target that is overexpressed in many NECs, including SCLC and epNECs, and is generally associated with poor clinical outcomes. Zocilurtatug pelitecan is a potential first-in-class DLL3-directed ADC.
The phase 3 DLLEVATE clinical trial (NCT07218146) is investigating zocilurtatug pelitecan monotherapy compared with investigator’s choice of therapy (topotecan [Hycamtin], lurbinectedin [Zepzelca], or amrubicin) in patients at least 18 years with relapsed SCLC who have previously received first-line platinum-based systemic therapy and had documented disease progression during or after their most recent systemic therapy.4 Patients who have received second-line tarlatamab are also permitted to enroll. Additional enrollment criteria include measurable disease per RECIST 1.1 criteria, adequate organ and marrow function, an ECOG performance status of 0 or 1, and a life expectancy of at least 3 months. Notably, patients with a history of treated and stable or untreated and asymptomatic central nervous system (CNS) metastases are permitted to enroll based on additional protocol criteria.
Patients will be excluded if they have received more than 1 prior line of systemic therapy for ES-SCLC, have received any prior ADC with a topoisomerase I inhibitor payload, have another known malignancy (exceptions are outlined in the protocol), have a history of or suspected interstitial lung disease or pneumonitis, have clinically severe pulmonary compromise as a result of intercurrent pulmonary illnesses, have received anti-cancer treatment within 3 weeks prior to the first study dose, have received prior radiotherapy, have unresolved toxicities of grade 2 or higher from previous anti-cancer treatment, have a known or active infection as defined in the protocol, or have clinically significant active cardiovascular disease or a history of an arterial thromboembolic event within 6 months before the first study dose.
The primary end points are overall response rate (ORR) per blinded independent central review (BICR), as well as overall survival. Secondary end points include duration of response, progression-free survival, and time to response as assessed by BICR and the investigators; investigator-assessed confirmed ORR; confirmed CNS response per BICR and the Response Assessment in Neuro-Oncology for Brain Metastases; treatment-emergent adverse effects; and quality of life outcomes.
