Tarlatamab, a first-in-class DLL3-targeted bispecific T cell engager, in recurrent small-cell lung cancer: an open-label, phase 1 study
Paz-Ares, L. Champiat, S. Lai, W. V. Izumi, H. Govindan, R. Boyer, M. Hummel, H. D. Borghaei, H. Johnson, M. L. Steeghs, N.
Paz-Ares, L.
Champiat, S.
Lai, W. V.
Izumi, H.
Govindan, R.
Boyer, M.
Hummel, H. D.
Borghaei, H.
Johnson, M. L.
Steeghs, N.
Citations
Altmetric:
Abstract
Purpose: Small cell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) is aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T cell engager molecule, binds both DLL3 and CD3 leading to T cell-mediated tumor lysis. Herein, we report phase 1 results of tarlatamab in patients with SCLC.
Patients and methods: This study evaluated tarlatamab in patients with relapsed/refractory SCLC. The primary endpoint was safety. Secondary endpoints included antitumor activity by modified RECIST 1.1, overall survival (OS), and pharmacokinetics.
Results: By July 19, 2022, 107 patients received tarlatamab in dose exploration (0.003 to 100 mg; n=73) and expansion (100 mg; n=34) cohorts. Median prior lines of anticancer therapy were 2 (range, 1-6); 49.5% received anti-programmed death-1/programmed death ligand-1 therapy. Any grade treatment-related adverse events (TRAEs) occurred in 97 patients (90.7%); grade ≥ 3 in 33 patients (30.8%). One patient (1%) had grade 5 pneumonitis. Cytokine release syndrome was the most common TRAE, occurring in 56 patients (52%) including grade 3 in 1 patient (1%). Maximum tolerated dose was not reached. Objective response rate (ORR) was 23.4% (95% CI: 15.7, 32.5) including 2 complete and 23 partial responses. Median duration of response was 12.3 months (95% CI: 6.6, 14.9). Disease control rate was 51.4% (95% CI: 41.5, 61.2). Median progression-free survival and OS were 3.7 months (95% CI: 2.1, 5.4) and 13.2 months (95% CI: 10.5, to not reached), respectively. Exploratory analysis suggests that selecting for increased DLL3 expression can result in increased clinical benefit.
Conclusion: In patients with heavily pretreated SCLC, tarlatamab demonstrated manageable safety with encouraging response durability. Further evaluation of this promising molecule is ongoing.
Authors
Paz-Ares, L.
Champiat, S.
Lai, W. V.
Izumi, H.
Govindan, R.
Boyer, M.
Hummel, H. D.
Borghaei, H.
Johnson, M. L.
Steeghs, N.
Blackhall, Fiona H
Dowlati, A.
Reguart, N.
Yoshida, T.
He, K.
Gadgeel, S. M.
Felip, E.
Zhang, Y.
Pati, A.
Minocha, M.
Mukherjee, S.
Goldrick, A.
Nagorsen, D.
Sadraei, N. H.
Owonikoko, T. K.
Champiat, S.
Lai, W. V.
Izumi, H.
Govindan, R.
Boyer, M.
Hummel, H. D.
Borghaei, H.
Johnson, M. L.
Steeghs, N.
Blackhall, Fiona H
Dowlati, A.
Reguart, N.
Yoshida, T.
He, K.
Gadgeel, S. M.
Felip, E.
Zhang, Y.
Pati, A.
Minocha, M.
Mukherjee, S.
Goldrick, A.
Nagorsen, D.
Sadraei, N. H.
Owonikoko, T. K.
Description
Date
2023
Publisher
Collections
Keywords
Type
Article
Citation
Paz-Ares L, Champiat S, Lai WV, Izumi H, Govindan R, Boyer M, et al. Tarlatamab, a first-in-class DLL3-targeted bispecific T cell engager, in recurrent small-cell lung cancer: an open-label, phase 1 study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Jan 23:101200JCO2202823. PubMed PMID: 36689692. Epub 2023/01/24. eng.