“The strong and durable antitumor activity we have observed with zoci, alongside a well-tolerated safety profile, highlights its potential to be a best-in-class, DLL3-targeted antibody-drug conjugate for small cell lung cancer,” said Rafael G. Amado, M.D., President, Head of Global Research and Development, Zai Lab. “Advancing this program from Phase 1 to a global, registrational study in less than two years reflects the speed, scientific rigor, and executional excellence of our team, and marks a major milestone for Zai Lab as we advance our global programs. Furthermore, we are rapidly expanding zoci’s development into other areas of high unmet need, including first-line small cell lung cancer and neuroendocrine carcinoma, both expected to enter the registrational phase next year.”

The presentation includes updated results from the Phase 1 monotherapy dose escalation and dose expansion portion of the study from 115 patients across six dose cohorts (0.8 mg/kg, 1.2 mg/kg, 1.6 mg/kg, 2.0 mg/kg, 2.4 mg/kg, and 2.8 mg/kg) as of the data cut-off date of September 15, 2025. 102 patients had the opportunity of at least one post-baseline tumor assessment per Response Evaluation Criteria in Solid Tumors version 1:1 (RECIST v1.1).

All patients in this multicenter study had progressed following platinum-based chemotherapy, and 90% of patients had progressed after immune checkpoint inhibitors. Of all patients, 44% had failed two prior lines of therapy, making this a highly pretreated population with limited therapeutic options. Eleven patients received a prior DLL3 bi-specific antibody. A total of 32% of patients had brain metastases at baseline. This study included patients in the United States, Spain, and China.

Key efficacy results include (n=102):

• Zoci demonstrated a high response rate across all dose levels in patients with ES-SCLC who progressed on or after platinum-based chemotherapy. Efficacy was consistent over time with additional patients and longer follow-up.
• In a subset of patients (n=53) receiving zoci as a second-line treatment, the best overall response rate (ORR) observed among patients in the 1.6 mg/kg arm (n=19) was 68%.
• A high response rate was also observed in patients (n=32) with brain metastasis at baseline, including an ORR of 80% for patients without prior brain radiotherapy.
• Three out of seven patients who progressed after prior tarlatamab, responded. Enrollment of tarlatamab pretreated patients continues.
• The estimated median duration of response (DoR) is 6.1 months, and median progression-free survival is 5.4 months across all doses and all lines of therapy. Responses were durable and clinically meaningful in this heavily pre-treated and difficult-to-treat population. In the dose finding cohort of the study, enrollment continues for 1.2 mg/kg and 1.6 mg/kg, with nearly half of responders still ongoing at data cut-off. Enrollment is expected to complete in Q4 2025.
• Responses occurred early in treatment with a median time to confirmed objective response of 6 weeks.

Key safety findings include (n=115):

• Zoci continues to demonstrate a well-tolerated safety profile with longer follow-up, particularly at the 1.2 or 1.6mg/kg dose level.
• In the 1.6 mg/kg dose cohort, Grade 3 or higher treatment-related adverse events (TRAE) occurred in 13% of patients and serious TRAEs occurred in 9%. No patients were discontinued due to toxicity.
• There were two cases of pneumonitis and interstitial lung disease, both Grade 1, in the 72 patients treated at 1.2 or 1.6 mg/kg dose.
• Across all dose cohorts, Grade 3 or higher TRAEs occurred in 20% of patients and serious TRAEs in 8%. The most common Grade 3 or higher TRAEs were anemia (10%) and neutropenia (11%). There were five patients who discontinued due to TRAEs, all in the higher dose levels.

“DLL3 represents a validated target in extensive-stage small cell lung cancer, where there is high need for new therapies given the disease’s aggressive nature and limited treatment options,” said Grace Dy, M.D., Roswell Park Comprehensive Cancer Center, Buffalo, NY, and study investigator. “These new Phase 1 results for zoci, including data that show rapid and sustained responses among the patient population, especially those with poor prognostic factors, are the latest clinical evidence that further demonstrate zoci’s potential as a differentiated, DLL3-targeted ADC.”

Global Phase 3 Registrational Study Opens for Patient Enrollment

The Phase 3 registrational clinical trial of zoci is a multicenter study that will enroll approximately 665 patients globally, including in North America, Asia, and Europe. The randomized, open-label study is designed to further evaluate the safety and efficacy of zoci compared to investigator’s choice single agent therapy (ICT) in patients with relapsed SCLC who have progressed on or after platinum-based first-line therapy as second-line therapy or one line of chemotherapy followed by tarlatamab. The primary endpoints are ORR assessed by Blinded Independent Central Review (BICR) per RECIST v1.1 for interim analysis and overall survival as the primary analysis. Secondary endpoints include duration of response, progression-free survival and safety.