SAPPHIRE: Phase III Study of Sitravatinib Plus Nivolumab Versus Docetaxel in Advanced Non-Squamous Non-Small Cell Lung Cancer.

Oct 23, 2023

Experts: H Borghaei,F de Marinis,D Dumoulin,C Reynolds,W S M E Theelen,I Percent,V Gutierrez Calderon,M L Johnson,A Madroszyk-Flandin,E B Garon,K He,D Planchard,M Reck,S Popat,R S Herbst,T A Leal,R L Shazer,X Yan,R Harrigan,S Peters

Checkpoint inhibitor (CPI) therapy revolutionized treatment for advanced non-small cell lung cancer (NSCLC); however, most patients progress due to primary or acquired resistance. Sitravatinib is a receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumor microenvironment towards an immunostimulatory state. Combining sitravatinib with nivolumab (sitra+nivo) may potentially overcome initial CPI resistance.
In the phase III SAPPHIRE study, patients with advanced non-oncogenic driven, non-squamous NSCLC who initially benefited from (≥4 months on CPI without progression) and subsequently experienced disease progression on or after CPI combined with or following platinum-based chemotherapy were randomized 1:1 to sitra (100 mg once daily orally)+nivo (240 mg every 2 weeks or 480 mg every 4 weeks intravenous) or docetaxel (75 mg/m every 3 weeks intravenous).
overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR; all assessed by blinded independent central review), and safety.
A total of 577 patients were randomized: sitra+nivo, n = 284; docetaxel, n = 293 (median follow-up, 17.1 months). Sitra+nivo did not significantly improve OS versus docetaxel (median, 12.2 versus 10.6 months; hazard ratio [HR] 0.86; 95% confidence interval [CI] 0.70-1.05; p = 0.144). Median PFS was 4.4 versus 5.4 months, respectively (HR 1.08; 95% CI 0.89-1.32; p = 0.452). ORR was 15.6%, sitra+nivo and 17.2%, docetaxel (p = 0.597); CBR was 75.5% and 64.5%, respectively (p = 0.004); median DOR was 7.4 versus 7.1 months, respectively (p = 0.924). Grade ≥3 treatment-related adverse events were observed in 53.0% versus 66.7% of patients receiving sitra+nivo versus docetaxel, respectively.
Although median OS was numerically longer with sitra+nivo, the primary endpoint was not met in patients with previously treated advanced non-squamous NSCLC. The safety profiles demonstrated were consistent with previous reports.

Copyright © 2023. Published by Elsevier Ltd.

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ABOUT THE EXPERTS

H Borghaei,F de Marinis,D Dumoulin,C Reynolds,W S M E Theelen,I Percent,V Gutierrez Calderon,M L Johnson,A Madroszyk-Flandin,E B Garon,K He,D Planchard,M Reck,S Popat,R S Herbst,T A Leal,R L Shazer,X Yan,R Harrigan,S Peters

H Borghaei

Hematology and Oncology Department, Fox Chase Cancer Center, Philadelphia, PA, USA. Electronic address: Hossein.Borghaei@fccc.edu.

F de Marinis

Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan, Italy.

D Dumoulin

Department of Pulmonary Medicine, Erasmus Medisch Centrum, Rotterdam, Netherlands.

C Reynolds

Florida Cancer Specialists and Research Institute – North Region (SCRI), Ocala, FL, USA.

W S M E Theelen

Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands.

I Percent

Florida Cancer Specialists and Research Institute – South Region (SCRI), Fort Myers, FL, USA.

V Gutierrez Calderon

Department of Medical Oncology, Hospital Regional Universitario de Málaga, Málaga, Spain.

M L Johnson

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

A Madroszyk-Flandin

Department of Medicine, Institut Paoli-Calmettes, Marseille, France.

E B Garon

Hematology-Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

K He

Comprehensive Cancer Center, Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, OH, USA.

D Planchard

Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.

M Reck

Department of Thoracic Oncology, LungenClinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.

S Popat

Lung Unit, Department of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, UK.

R S Herbst

Medical Oncology, Yale University, New Haven, CT, USA.

T A Leal

Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.

R L Shazer

Department of Clinical Research and Development, Mirati Therapeutics, Inc., San Diego, CA, USA.

X Yan

Department of Clinical Research and Development, Mirati Therapeutics, Inc., San Diego, CA, USA.

R Harrigan

Department of Clinical Research and Development, Mirati Therapeutics, Inc., San Diego, CA, USA.

S Peters

Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.