Scott J Antonia1, Ani Balmanoukian2, Julie Brahmer3, Sai-Hong I Ou4, Matthew D Hellmann5, Sang-We Kim6, Myung-Ju Ahn7, Dong-Wan Kim8, Martin Gutierrez9, Stephen V Liu10, Patrick Schöffski11, Dirk Jäger12, Rahima Jamal13, Guy Jerusalem14, Jose Lutzky15, John Nemunaitis16, Luana Calabrò17, Jared Weiss18, Shirish Gadgeel19, Jaishree Bhosle20, Paolo A Ascierto21, Marlon C Rebelatto22, Rajesh Narwal22, Meina Liang22, Feng Xiao22, Joyce Antal22, Shaad Abdullah22, Natasha Angra22, Ashok K Gupta22, Samir N Khleif23, Neil H Segal5. 1. Moffitt Cancer Center, Tampa, Florida. Electronic address: Scott.Antonia@Moffitt.org. 2. The Angeles Clinic and Research Institute, Los Angeles, California. 3. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland. 4. Department of Medicine, Division of Hematology-Medical Oncology, University of California Irvine School of Medicine, Irvine, California. 5. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 6. Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 7. Sunkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea. 8. Seoul National University Hospital, Seoul, South Korea. 9. Hackensack University Medical Center, Hackensack, New Jersey. 10. Georgetown University Medical Center, Washington, DC. 11. University Hospitals Leuven, Leuven, Belgium. 12. Nationales Centrum für Tumorerkrankungen Heidelberg, Heidelberg, Baden-Württemberg, Germany. 13. Hôpital Notre-Dame, CHUM, University of Montréal, CHUM Research Center (CRCHUM), Montreal, Quebec, Canada. 14. CHU Sart Tilman Liège and Liège University, Liège, Belgium. 15. Mount Sinai Comprehensive Cancer Center, Miami Beach, Florida. 16. University of Toledo College of Medicine and Life Sciences, Toledo, Ohio. 17. Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy. 18. University of North Carolina Hospitals, Chapel Hill, North Carolina. 19. University of Michigan, Ann Arbor, Michigan. 20. Royal Marsden NHS Foundation Trust, London, United Kingdom. 21. Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy. 22. AstraZeneca, Gaithersburg, Maryland. 23. Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical School, Washington, DC.
Abstract
INTRODUCTION: Durvalumab is a selective, high-affinity human immunoglobulin G1 monoclonal antibody that blocks programmed cell death ligand 1 (PD-L1) binding to programmed death 1. Here we report safety and clinical activity in the NSCLC cohort of a phase I/II trial that included multiple tumor types (Study 1108; NCT01693562). METHODS: Patients with stage IIIB-IV NSCLC (squamous or nonsquamous) received durvalumab 10 mg/kg every 2 weeks for 12 months or until confirmed progressive disease or unacceptable toxicity. Primary objectives were safety and antitumor activity. Tumoral PD-L1 expression was assessed using the VENTANA SP263 Assay. Responses were assessed by blinded independent central review (Response Evaluation Criteria in Solid Tumors v1.1). Adverse events were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events (v4.03). RESULTS: Of 304 patients, 79.0% were previously treated. Confirmed objective response rate was 21.8% in patients with greater than or equal to 25% PD-L1 expression and 6.4% in those with less than 25%; 25.9% in first-line patients and 12.7% in previously treated patients; and 14.0% in squamous and 16.7% in nonsquamous disease. Median overall survival was 12.4 months and median progression-free survival was 1.7 months; both were numerically longer in the PD-L1 greater than or equal to 25% group than in the PD-L1 less than 25% group (overall survival 16.4 versus 7.6 months, respectively; progression-free survival 2.6 versus 1.4 months, respectively). Treatment-related adverse events occurred in 57.2%, were grade 3/4 in 10.2%, and led to discontinuation in 5.6%. One patient (0.3%) died of treatment-related pneumonia with underlying pneumonitis. CONCLUSIONS: Durvalumab was clinically active irrespective of histology in this mostly pretreated population, with a manageable safety profile. Response rates and survival appeared to be enhanced in patients with greater tumoral PD-L1 expression.
INTRODUCTION:Durvalumab is a selective, high-affinity human immunoglobulin G1 monoclonal antibody that blocks programmed cell death ligand 1 (PD-L1) binding to programmed death 1. Here we report safety and clinical activity in the NSCLC cohort of a phase I/II trial that included multiple tumor types (Study 1108; NCT01693562). METHODS:Patients with stage IIIB-IV NSCLC (squamous or nonsquamous) received durvalumab 10 mg/kg every 2 weeks for 12 months or until confirmed progressive disease or unacceptable toxicity. Primary objectives were safety and antitumor activity. Tumoral PD-L1 expression was assessed using the VENTANA SP263 Assay. Responses were assessed by blinded independent central review (Response Evaluation Criteria in Solid Tumors v1.1). Adverse events were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events (v4.03). RESULTS: Of 304 patients, 79.0% were previously treated. Confirmed objective response rate was 21.8% in patients with greater than or equal to 25% PD-L1 expression and 6.4% in those with less than 25%; 25.9% in first-line patients and 12.7% in previously treated patients; and 14.0% in squamous and 16.7% in nonsquamous disease. Median overall survival was 12.4 months and median progression-free survival was 1.7 months; both were numerically longer in the PD-L1 greater than or equal to 25% group than in the PD-L1 less than 25% group (overall survival 16.4 versus 7.6 months, respectively; progression-free survival 2.6 versus 1.4 months, respectively). Treatment-related adverse events occurred in 57.2%, were grade 3/4 in 10.2%, and led to discontinuation in 5.6%. One patient (0.3%) died of treatment-related pneumonia with underlying pneumonitis. CONCLUSIONS:Durvalumab was clinically active irrespective of histology in this mostly pretreated population, with a manageable safety profile. Response rates and survival appeared to be enhanced in patients with greater tumoral PD-L1 expression.
Authors: S Miwa; T Nojima; A A Alomesen; H Ikeda; N Yamamoto; H Nishida; K Hayashi; A Takeuchi; K Igarashi; T Higuchi; H Yonezawa; Y Araki; S Morinaga; Y Asano; H Tsuchiya Journal: Clin Transl Oncol Date: 2021-02-26 Impact factor: 3.405
Authors: Rajaa El Meskini; Devon Atkinson; Alan Kulaga; Abdalla Abdelmaksoud; Michelle Gumprecht; Nathan Pate; Susana Hayes; Michael Oberst; Ian M Kaplan; Patrick Raber; Terry Van Dyke; Shyam K Sharan; Robert Hollingsworth; Chi-Ping Day; Glenn Merlino; Zoë Weaver Ohler Journal: Mol Cancer Res Date: 2021-04-22 Impact factor: 6.333