First DLL3-targeted therapy shows promise in SCLC

Tarlatamab, the first delta-like ligand 3 (DLL3)-targeted immune therapy, demonstrated encouraging anti-tumour activity and an acceptable safety profile in patients with heavily pre-treated small cell lung cancer (SCLC). The results of the current phase 1 trial initiated the development of the phase 2 DeLLphi-301 study, analysing tarlatamab in patients with SCLC who received at least 2 prior lines of therapy [1].

“The treatment options for patients with pre-treated SCLC are limited,” stated Prof. Hossein Borghaei (Fox Chase Cancer Center, PA, USA). “Therefore, novel therapies are urgently needed for these patients.” Tarlatamab is a bispecific T cell-engager immune therapy that binds both DLL3 and CD3 [2]. The first-in-human study of tarlatamab evaluated this agent in 106 patients with SCLC who progressed on at least 1 platinum-based chemotherapy regimen. Safety was the primary outcome of this trial, in which patients received tarlatamab doses of up to 100 mg per 2 weeks, intravenously administered.

“The safety profile was acceptable across the administered doses of tarlatamab,” commented Prof. Borghaei. Cytokine release syndrome (CRS) occurred in 53% of the patients; all but one of the cases were categorised as grade 1 or 2. In addition, CRS events occurred in cycle 1 and rarely recurred in following cycles. Pyrexia (38%), dysgeusia (23%), fatigue (22%), and nausea (20%) were other common adverse events (AEs), mostly being grade 1 or 2 events. Neurologic events (7%), mostly confusion, and neutropenia (9%) were the most frequently reported grade 3 events. In total, 4 patients discontinued the experimental treatment due to treatment-related AEs: 1 case of encephalopathy, 1 case of neurotoxicity, and 2 cases of pneumonitis.

The confirmed objective response rate was 23%, representing 2 complete responses and 22 partial responses. The median duration of response among those with a confirmed response was 13.0 months, with a median time to response of 1.8 months. Furthermore, the disease control rate was 52%, the median progression-free survival was 3.7 months, and the median overall survival was 13.2 months. Of note, 37% of the patients had a target lesion shrinkage of more than 30%. Following these results, the phase 2 DeLLphi-301 trial (NCT05060016) has been launched to further explore the possibilities of tarlatamab in patients with pre-treated SCLC.

1. Borghaei H, et al. Phase 1 updated exploration and first expansion data for DLL3-Targeted T-cell engager tarlatamab in SCLC (DeLLphi-300 Study). OA12.05, WCLC 2022, 06–09 August.
2. Giffin MJ, et al. Clin Cancer Res. 2021;27:1526-1537

 

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Posted on 23 August, 202225 March, 2024