Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer
Impressive improvement in overall survival when comparing 55 vs 33 months and progression-free survival (almost double) due to tolerable toxicity. Now in NCCN guidelines…
Sustained Clinical Benefit and Intracranial Activity of Tarlatamab in Previously Treated Small Cell Lung Cancer: DeLLphi-300 Trial Update
Author(s): Afshin Dowlati, MD1; Horst-Dieter Hummel, MD2; Stephane Champiat, MD, PHD3; Maria Eugenia Olmedo, MD, PhD4; Michael Boyer, MB, BS, PHD5,6; Kai He, MD, PHD7; Neeltje Steeghs, MD, PHD8; Hiroki Izumi, MD, PHD9; Melissa L. Johnson, MD10; Tatsuya Yoshida, MD, PHD11; Hasna Bouchaab, MD12; Hossein Borghaei, DO13; Enriqueta Felip, MD, PHD14; Philipp J. Jost, MD15; Shirish Gadgeel, MD16; Xi Chen, MD, PHD17; Youfei Yu, PHD17; Pablo Martinez, MD, PhD17; Amanda Parkes, MD17; Luis Paz-Ares, MD, PHD18
Source: https://doi.org/10.1200/JCO.24.00553
Dr. Maen Hussein's Thoughts
Improved outcome in patients with brain metastases, but only uses a small number. It is still promising.
ABSTRACT
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.
Author Affiliations
1University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, OH; 2Translational Oncology/Early Clinical Trial Unit (ECTU), Bavarian Cancer Research Center, National Center for Tumor Diseases, Comprehensive Cancer Center Mainfranken and University Hospital Würzburg, Würzburg, Germany; 3Department of Therapeutic Innovation and Early Phase Trials, Gustave Roussy, Villejuif, France; 4Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid, Spain; 5Department of Medical Oncology, Chris O’Brien Lifehouse, Sydney, Australia; 6Faculty of Medicine and Health, School of Medicine, University of Sydney, Sydney, Australia; 7Comprehensive Cancer Center, Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, OH; 8Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands; 9Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan; 10Department of Medical Oncology, Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN; 11Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; 12Department of Oncology, Vaud University Hospital, Lausanne, Switzerland; 13Fox Chase Cancer Center, Philadelphia, PA; 14Department of Medical Oncology, Hospital Universitario del Vall d’Hebron, Barcelona, Spain; 15Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria; 16Division of Hematology and Oncology, Department of Internal Medicine, Henry Ford Cancer Institute/Henry Ford Health System, Detroit, MI; 17Amgen Inc, Thousand Oaks, CA; 18Hospital Universitario 12 de Octubre, CNIO-H12o Lung Cancer Unit, Complutense University and Ciberonc, Madrid, SpainRelated Articles
Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer
Very interesting study using tarlatamab, a bispecific T-cell engager that directs T-cells to malignant cells expressing delta-like ligand 3 (DLL3). This was a dose escalation phase II, ORR was 40% and the longevity of response in responders was impressive for this disease. Further studies are sure to come.
