Updated results of the randomized phase 2 dose optimization study of alveltamig (ZG006), a trispecific T cell engager targeting DLL3/DLL3/CD3, as monotherapy in patients with advanced small cell lung cancer.

Abstract

8109 Background: Alveltamig (ZG006) is a trispecific T cell engager (Tri-TE) targeting Delta-like ligand 3 (DLL3) and CD3, designed to bridge tumor cells and T cells by binding to two distinct DLL3 epitopes on tumor cells and CD3 on T cells, thereby mediating T cell-specific killing of DLL3-expressing tumor cells such as small cell lung cancer (SCLC). Methods: This is a multicenter, randomized, open-label, phase 2 dose-optimization study. Patients with SCLC who have failed at least two prior lines of standard therapy are randomized 1:1 to receive ZG006 at either 10 mg or 30 mg Q2W (both with a 1 mg priming dose). Based on the prior data from dose optimization in this study with an objective response rate (ORR) at 53.3% and median progression-free survival (PFS) at 7.03 months in the 10 mg group, 10 mg Q2W was selected as the recommended dose schedule for ongoing pivotal studies in advanced SCLC. Here we present the updated efficacy data with longer follow up and key subgroup analyses from this study. Results: This analysis included 60 treated patients (30 each from 10 and 30 mg group). With a median follow-up of about 13.5 months, the median duration of response (DoR) was not mature with 9-month DoR rates reaching 61.6% and 58.4% for 10 mg and 30 mg respectively. Likewise, the median OS for both groups was not reached, however, 12-month OS rates for two groups have approached 65.9% and 59.2% respectively. Based on the IRC data as of Sept 30, 2025, for the 10 mg and 30 mg groups, patients with previously treated and stable brain metastases at baseline achieved a confirmed ORR of 50.0% (4/8) and 44.4% (4/9), respectively, while patients without baseline brain metastases had an ORR of 54.5% (12/22) and 61.9% (13/21). Patients presented with baseline liver metastases achieved an ORR of 58.3% (7/12) and 46.2% (6/13), compared with 50.0% (9/18) and 64.7% (11/17) in patients without liver metastases. While 27 patients in 10 mg and 24 patients in 30 mg had previously received immune checkpoint inhibitors, a notable ORR of 55.6% (15/27) and 58.3% (14/24) was observed. Among patients with exactly two prior lines of systemic therapy, the ORRs were 50.0% (8/16) and 64.7% (11/17), whereas those who had received three or more prior lines demonstrated an ORR of 57.1% (8/14) and 46.2% (6/13) in 10 and 30 mg groups. Conclusions: With longer follow up, both ZG006 10 mg Q2W and 30 mg Q2W continued to demonstrate robust antitumor activity with a trend of longer DoR and OS in patients with relapsed or refractory SCLC. Subgroup analyses demonstrated consistent antitumor activity across key prognostic subgroups including those with baseline treated brain metastases, those with baseline liver metastases, and those who received multiple lines of prior systemic treatment. These results also support further development of ZG006 in SCLC with ongoing pivotal studies. Clinical trial information: NCT06283719 .