Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study

Luis Paz-Ares, Stephane Champiat, W. Victoria Lai, Hiroki Izumi, Ramaswamy Govindan, Michael Boyer, Horst Dieter Hummel, Hossein Borghaei, Melissa L. Johnson, Neeltje Steeghs, Fiona Blackhall, Afshin Dowlati, Noemi Reguart, Tatsuya Yoshida, Kai He, Shirish M. Gadgeel, Enriqueta Felip, Yiran Zhang, Amrita Pati, Mukul MinochaSujoy Mukherjee, Amanda Goldrick, Dirk Nagorsen, Nooshin Hashemi Sadraei, Taofeek K. Owonikoko

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

PURPOSESmall-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-cellb-mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC.PATIENTS AND METHODSThis study evaluated tarlatamab in patients with relapsed/refractory SCLC. The primary end point was safety. Secondary end points included antitumor activity by modified RECIST 1.1, overall survival, and pharmacokinetics.RESULTSBy 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 antiprogrammed death-1/programmed death ligand-1 therapy. Any-grade treatment-related adverse events occurred in 97 patients (90.7%) and grade b % 3 in 33 patients (30.8%). One patient (1%) had grade 5 pneumonitis. Cytokine release syndrome was the most common treatment-related adverse event, occurring in 56 patients (52%) including grade 3 in one patient (1%). Maximum tolerated dose was not reached. Objective response rate was 23.4% (95% CI, 15.7 to 32.5) including two complete and 23 partial responses. The median duration of response was 12.3 months (95% CI, 6.6 to 14.9). The disease control rate was 51.4% (95% CI, 41.5 to 61.2). The median progression-free survival and overall survival were 3.7 months (95% CI, 2.1 to 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.CONCLUSIONIn patients with heavily pretreated SCLC, tarlatamab demonstrated manageable safety with encouraging response durability. Further evaluation of this promising molecule is ongoing.

Original languageEnglish
Pages (from-to)2893-2903
Number of pages11
JournalJournal of Clinical Oncology
Volume41
Issue number16
DOIs
StatePublished - Jun 1 2023

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