TY - JOUR
T1 - Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer
T2 - An Open-Label, Phase I Study
AU - Paz-Ares, Luis
AU - Champiat, Stephane
AU - Lai, W Victoria
AU - Izumi, Hiroki
AU - Govindan, Ramaswamy
AU - Boyer, Michael
AU - Hummel, Horst-Dieter
AU - Borghaei, Hossein
AU - Johnson, Melissa L
AU - Steeghs, Neeltje
AU - Blackhall, Fiona
AU - Dowlati, Afshin
AU - Reguart, Noemi
AU - Yoshida, Tatsuya
AU - He, Kai
AU - Gadgeel, Shirish M
AU - Felip, Enriqueta
AU - Zhang, Yiran
AU - Pati, Amrita
AU - Minocha, Mukul
AU - Mukherjee, Sujoy
AU - Goldrick, Amanda
AU - Nagorsen, Dirk
AU - Hashemi Sadraei, Nooshin
AU - Owonikoko, Taofeek K
PY - 2023/6/1
Y1 - 2023/6/1
N2 - 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-cellb-mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC.PATIENTS AND METHODS: This 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.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 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.CONCLUSION: In patients with heavily pretreated SCLC, tarlatamab demonstrated manageable safety with encouraging response durability. Further evaluation of this promising molecule is ongoing.
AB - 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-cellb-mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC.PATIENTS AND METHODS: This 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.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 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.CONCLUSION: In patients with heavily pretreated SCLC, tarlatamab demonstrated manageable safety with encouraging response durability. Further evaluation of this promising molecule is ongoing.
KW - Humans
KW - Ligands
KW - Neoplasm Recurrence, Local/drug therapy
KW - Small Cell Lung Carcinoma
KW - Antineoplastic Agents/adverse effects
KW - Lung Neoplasms/pathology
KW - T-Lymphocytes
KW - Membrane Proteins
KW - Intracellular Signaling Peptides and Proteins/therapeutic use
UR - https://www.scopus.com/pages/publications/85159344990
U2 - 10.1200/JCO.22.02823
DO - 10.1200/JCO.22.02823
M3 - Article
C2 - 36689692
SN - 0732-183X
VL - 41
SP - 2893
EP - 2903
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 16
ER -
