Amgen's Bispecific Therapy Tarlatamab Shows 40% Objective Response Rate in Heavily Pretreated Small Cell Lung Cancer, Phase 2 Data Reveal

▎WuXi

Edited by Kant Content Team

Amgen announced today the results of a global phase 2 clinical trial for tarlatamab, an investigational bispecific T-cell engager (BiTE), in patients with advanced small cell lung cancer (SCLC) who have received two or more prior treatments. The trial results showed,In patients with advanced SCLC, tarlatamab achieved an objective response rate (ORR) of 40% and a median overall survival of 14.3 months.. Detailed data were published in The New England Journal of Medicine (NEJM).

SCLC is one of the most aggressive solid tumors, with a median survival of approximately 12 months after initial treatment and a 5-year relative survival rate of 7% for all stages. Despite high initial response rates to first-line platinum-based chemotherapy, patients quickly develop resistance to second-line and subsequent treatments. Moreover, there are currently no approved treatment options available for third-line therapy in SCLC.

Tarlatamab is an investigational targeted immunotherapy designed by Amgen researchers. It works by simultaneously binding to CD3 on T cells and DLL3 on SCLC cells, bringing the patient's own T cells into close proximity with SCLC cells. This leads to the formation of immune synapses and the lysis of cancer cells.DLL3 is an exciting target for the treatment of small cell lung cancer because approximately 85% to 94% of patients express DLL3 on the surface of small cell lung cancer cells, while it is minimally expressed in normal cells.

The data from this Phase 2 clinical trial shows,At a median follow-up of 10.6 months, an intent-to-treat analysis of 100 patients receiving the selected 10 mg dose of tarlatamab showed an ORR of 40% (97.5% CI: 29, 52).For the key secondary endpoints, the median progression-free survival (mPFS) was 4.9 months (95% CI: 2.9, 6.7), and the median overall survival was 14.3 months (95% CI: 10.8, NE).Among patients who responded to the 10 mg dose of tarlatamab, 58% had a response lasting at least 6 months at the data cutoff, and 55% of the responses were still ongoing.

In terms of safety, no new safety signals were observed compared to Phase 1 clinical trials. Discontinuation due to treatment-related adverse events (TRAE) was uncommon (4%). The most common treatment-emergent adverse events (TEAE) reported in patients in the tarlatamab 10 mg group were cytokine release syndrome (CRS; 49%), fever (38%), decreased appetite (25%), and dysgeusia (24%). CRS was primarily limited to the first and second doses, mostly Grade 1 or 2, and generally manageable with supportive care. In the tarlatamab 10 mg dose group, the incidence of Grade 3 CRS was low (0%), and no Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) or related neurological events were observed (0%). The NEJM paper reported one patient death, which was considered treatment-related.

References:

[1] AMGEN PRESENTS NEW TARLATAMAB DATA IN SMALL CELL LUNG CANCER. Retrieved October 20, 2023, from https://www.prnewswire.com/news-releases/amgen-presents-new-tarlatamab-data-in-small-cell-lung-cancer-301963139.html

[2] Ahn et al., (2023). Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. New England Journal of Medicine, DOI: 10.1056/NEJMoa2307980