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

Author:

Paz-Ares Luis1ORCID,Champiat Stephane2ORCID,Lai W. Victoria3ORCID,Izumi Hiroki4ORCID,Govindan Ramaswamy5ORCID,Boyer Michael6ORCID,Hummel Horst-Dieter7,Borghaei Hossein8ORCID,Johnson Melissa L.9ORCID,Steeghs Neeltje10ORCID,Blackhall Fiona11,Dowlati Afshin12ORCID,Reguart Noemi13ORCID,Yoshida Tatsuya14ORCID,He Kai15ORCID,Gadgeel Shirish M.16ORCID,Felip Enriqueta17ORCID,Zhang Yiran18ORCID,Pati Amrita18,Minocha Mukul18,Mukherjee Sujoy18,Goldrick Amanda18,Nagorsen Dirk18,Hashemi Sadraei Nooshin18ORCID,Owonikoko Taofeek K.19ORCID

Affiliation:

1. Hospital Universitario 12 de Octubre, CNIO-H120 Lung Cancer Unit, Ciberonc and Universidad Complutense, Madrid, Spain

2. Gustave Roussy, DC(c)partement d'Innovation ThC(c)rapeutique et d'Essais PrC(c)coces (DITEP), Villejuif, France

3. Thoracic Oncology Service, Department of Medicine, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, NY

4. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan

5. Divisions of Hematology and Oncology, Washington University Medical School, St Louis, MO

6. Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia

7. Translational Oncology/Early Clinical Trial Unit (ECTU), Comprehensive Cancer Center Mainfranken, University Hospital Wuerzburg, Wuerzburg, Germany

8. Fox Chase Cancer Center, Philadelphia, PA

9. Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN

10. Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands

11. Department of Medical Oncology, The Christie NHS Foundation Trust, Division of Cancer Sciences, University of Manchester, Manchester, UK

12. Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, OH

13. Department of Medical Oncology, Thoracic Oncology Unit, IDIBAPS, Hospital Clinic, University of Barcelona School of Medicine, Barcelona, Spain

14. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan

15. Division of Medical Oncology, James Thoracic Oncology Center, The Ohio State University Comprehensive Cancer Center, Columbus, OH

16. Henry Ford Cancer Institute, Detroit, MI

17. Medical Oncology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain

18. Amgen, Inc, Thousand Oaks, CA

19. UPMC Hillman Cancer Center, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA

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-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. [Media: see text]

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3