Zai Lab and Amgen Inc. launch a global Phase 1b trial combining zocilurtatug pelitecan (zoci) with IMDELLTRA® in extensive-stage small cell lung cancer, targeting DLL3 with a dual ADC and BiTE® approach.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
Zai Lab Limited has announced a global clinical trial collaboration and supply agreement with Amgen Inc. to evaluate zocilurtatug pelitecan (zoci, formerly ZL-1310), a DLL3-targeting antibody-drug conjugate (ADC), in combination with Amgen’s IMDELLTRA® (tarlatamab-dlle), a DLL3-targeting bispecific T-cell engager (BiTE®) therapy, in patients with extensive-stage small cell lung cancer (ES-SCLC).
Amgen will sponsor and conduct the global Phase 1b study assessing safety and efficacy of the combination, while Zai Lab retains full rights to zoci and will supply the drug.
The Phase 1b trial targets ES-SCLC patients, leveraging complementary mechanisms: zoci delivers a cytotoxic topoisomerase 1 inhibitor payload selectively to DLL3-expressing tumor cells, while IMDELLTRA® binds DLL3 and CD3 to activate T-cells against tumors. This dual approach aims to deepen responses, including intracranial activity, and overcome resistance in this aggressive disease.
Rafael G. Amado, M.D., President and Head of Global R&D at Zai Lab, stated: “In combination, this dual-targeting strategy has the potential to increase the rate and deepen responses both systemically and, in the brain, address resistance pathways, and unlock new treatment paradigms for patients with small cell lung cancer.”
Zoci, built on the TMALIN® platform, uses a novel camptothecin derivative payload engineered to exploit the tumor microenvironment, minimizing off-target toxicity. It has FDA Orphan Drug and Fast Track Designations for SCLC and is in multiple trials, including the pivotal global Phase 3 DLLEVATE study (NCT07218146) versus investigator’s choice in relapsed ES-SCLC.
IMDELLTRA® received FDA traditional approval on November 19, 2025, for ES-SCLC after platinum-based chemotherapy progression, based on the DeLLphi-304 Phase 3 trial.
Phase 1/2 data for zoci (NCT06179069), updated as of September 15, 2025, and presented at ASCO 2025 and AACR-NCI-EORTC 2025, showed high overall response rates (ORR) in heavily pretreated ES-SCLC patients (90% post-immunotherapy, 44% ≥2 prior lines).
In second-line at 1.6 mg/kg (n=19), ORR was 68%; in baseline brain metastases (n=32), ORR reached 80% without prior brain radiotherapy. Median duration of response was 6.1 months, with a manageable profile (13% Grade ≥3 treatment-related adverse events at 1.6 mg/kg, no discontinuations). Responses occurred rapidly (median 6 weeks), including post-tarlatamab failures.
Small cell lung cancer accounts for 15% of 2.5 million annual global lung cancer cases, with two-thirds diagnosed at extensive-stage and median survival 12 months post-initial therapy. Prognosis is poor (5-10% 5-year survival), with limited post-progression options beyond platinum-etoposide ± immunotherapy.
This collaboration underscores DLL3 as a key target, potentially advancing beyond chemotherapy paradigms.
References
Zai Lab Announces Global Clinical Trial Collaboration and Supply Agreement to Evaluate Novel DLL3 ADC, Zocilurtatug Pelitecan, in Combination with a Bispecific T-cell Engager Therapy, 01 March 2026, Zai Lab Announces Global Clinical Trial Collaboration and Supply Agreement to Evaluate Novel DLL3 ADC, Zocilurtatug Pelitecan, in Combination with a Bispecific T-cell Engager Therapy – Zai Lab Limited
A Study of ZL-1310 in Subjects with Small Cell Lung Cancer, ClinicalTrials.gov ID NCT06179069, https://clinicaltrials.gov/study/NCT06179069
A Study of ZL-1310 Versus Investigator’s Choice of Therapy in Participants with Relapsed Small Cell Lung Cancer (DLLEVATE) (DLLEVATE), ClinicalTrials.gov ID NCT07218146, https://clinicaltrials.gov/study/NCT07218146
About the Writer
Chikkula Pavan Kumar, PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.