TY - JOUR
T1 - Sustained Clinical Benefit and Intracranial Activity of Tarlatamab in Previously Treated Small Cell Lung Cancer
T2 - DeLLphi-300 Trial Update
AU - Dowlati, Afshin
AU - Hummel, Horst-Dieter
AU - Champiat, Stephane
AU - Olmedo, Maria Eugenia
AU - Boyer, Michael
AU - He, Kai
AU - Steeghs, Neeltje
AU - Izumi, Hiroki
AU - Johnson, Melissa L
AU - Yoshida, Tatsuya
AU - Bouchaab, Hasna
AU - Borghaei, Hossein
AU - Felip, Enriqueta
AU - Jost, Philipp J
AU - Gadgeel, Shirish
AU - Chen, Xi
AU - Yu, Youfei
AU - Martinez, Pablo
AU - Parkes, Amanda
AU - Paz-Ares, Luis
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2024/10/10
Y1 - 2024/10/10
N2 - Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3, has shown durable anticancer activity and manageable safety in previously treated small cell lung cancer (SCLC) in DeLLphi-300 phase I and DeLLphi-301 phase II trials. Here, we report extended follow-up of DeLLphi-300 (median follow-up, 12.1 months [range, 0.2-34.3]) in fully enrolled cohorts treated with tarlatamab ≥10 mg dose administered once every two weeks, once every three weeks, or once on day 1 and once on day 8 of a 21-day cycle (N = 152). Overall, the objective response rate (ORR) was 25.0%; the median duration of response (mDOR) was 11.2 months (95% CI, 6.6 to 22.3), and the median overall survival (mOS) was 17.5 months (95% CI, 11.4 to not estimable [NE]). Among 17 patients receiving 10 mg tarlatamab once every two weeks, the ORR was 35.3%, the mDOR was 14.9 months (95% CI, 3.0 to NE), the mOS was 20.3 months (95% CI, 5.1 to NE), and 29.4% had sustained disease control with time on treatment ≥52 weeks. No new safety signals were identified. In modified Response Assessment in Neuro-Oncology Brain Metastases analyses, CNS tumor shrinkage of ≥30% was observed in 62.5% of patients (10 of 16) who had a baseline CNS lesion of ≥10 mm, including in a subset of patients with tumor shrinkage long after previous brain radiotherapy. In DeLLphi-300 extended follow-up, tarlatamab demonstrated unprecedented survival and potential findings of intracranial activity in previously treated SCLC.
AB - Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3, has shown durable anticancer activity and manageable safety in previously treated small cell lung cancer (SCLC) in DeLLphi-300 phase I and DeLLphi-301 phase II trials. Here, we report extended follow-up of DeLLphi-300 (median follow-up, 12.1 months [range, 0.2-34.3]) in fully enrolled cohorts treated with tarlatamab ≥10 mg dose administered once every two weeks, once every three weeks, or once on day 1 and once on day 8 of a 21-day cycle (N = 152). Overall, the objective response rate (ORR) was 25.0%; the median duration of response (mDOR) was 11.2 months (95% CI, 6.6 to 22.3), and the median overall survival (mOS) was 17.5 months (95% CI, 11.4 to not estimable [NE]). Among 17 patients receiving 10 mg tarlatamab once every two weeks, the ORR was 35.3%, the mDOR was 14.9 months (95% CI, 3.0 to NE), the mOS was 20.3 months (95% CI, 5.1 to NE), and 29.4% had sustained disease control with time on treatment ≥52 weeks. No new safety signals were identified. In modified Response Assessment in Neuro-Oncology Brain Metastases analyses, CNS tumor shrinkage of ≥30% was observed in 62.5% of patients (10 of 16) who had a baseline CNS lesion of ≥10 mm, including in a subset of patients with tumor shrinkage long after previous brain radiotherapy. In DeLLphi-300 extended follow-up, tarlatamab demonstrated unprecedented survival and potential findings of intracranial activity in previously treated SCLC.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Brain Neoplasms/drug therapy
KW - Female
KW - Humans
KW - Lung Neoplasms/drug therapy
KW - Male
KW - Middle Aged
KW - Small Cell Lung Carcinoma/drug therapy
UR - http://www.scopus.com/inward/record.url?scp=85204066249&partnerID=8YFLogxK
U2 - 10.1200/JCO.24.00553
DO - 10.1200/JCO.24.00553
M3 - Article
C2 - 39208379
SN - 0732-183X
VL - 42
SP - 3392
EP - 3399
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 29
M1 - 10.1200/JCO.24.00553
ER -