8096 Background: Alveltamig (ZG006) is a uniquely designed T cell engager, targeting two distinct delta-like ligand 3 (DLL3) epitopes and CD3 and, thereby bridging tumor cells and T cells together and mediating T cell-specific killing of DLL3-expressing tumor cells such as small cell lung cancer (SCLC) or neuroendocrine carcinoma (NEC). Methods: This is a multi-center, open-label, phase 1 clinical study of ZG006 as monotherapy in patients with SCLC or NEC who failed or were intolerant to the standard therapies. A standard "3+3" design, with an accelerated titration approach for the first two lower dose levels was used during the dose escalation stage. Here we report the updated results of the efficacy and safety data from the phase I study. Results: In this phase I study, patients received ZG006 at 0.1 mg Q2W and escalated at 8 dose levels up to 100 mg Q2W (Wang Q et al, ASCO 2025). A step dose of 1 mg was implemented for higher dose groups starting from 10 mg Q2W. Dose expansion was conducted at dose levels of 10, 30, and 60 mg. A total of 31 patients with SCLC, including 4, 15, and 12 patients from the 10 mg, 30 mg, and 60 mg dose groups respectively, were included in the current efficacy analysis. The overall median follow-up time was approximately 16 months. The median age was 59 years (range, 45.0-72.0), the median number of prior treatment lines was 3 (range,1-4), 80.6% of the patients had received prior immunotherapy, and 90.3% had a baseline ECOG performance status score of 1. The confirmed objective response rate (ORR) assessed by an independent review committee (IRC) was 74.2%. The median duration of response (DoR) was 12.6 months, with 12-month DoR rate at 65.3 %. The estimated 12-month PFS rate was 50.5%. The median overall survival (OS) was not reached yet, however,the 12-month and 18-month OS rates approached 74.2% and 58.6% respectively. Consistent with prior report, the most common adverse events with longer follow-up included CRS, anemia and other conditions, with most being Grade 1 or 2 and occurring during the first two cycles. Overall, ZG006 was well-tolerated and the treatment related adverse events including CRS were manageable. Conclusions: With longer follow up from phase I study, ZG006 continued to demonstrate robust antitumor activity in the dose expansion cohorts including high ORR, longer DoR/PFS, and clinically meaningful survival benefits in patients with refractory SCLC. No new safety signal was encountered. These data support ongoing development of ZG006 as monotherapy and in combination with other modalities in SCLC. Clinical trial information: NCT05978284 .
Wang et al. (Thu,) studied this question.