Roy S Herbst1, Hendrik Tobias Arkenau2, Johanna Bendell3, Edward Arrowsmith4, Martin Wermke5, Andres Soriano6, Nicolas Penel7, Rafael Santana-Davila8, Helge Bischoff9, Ian Chau10, Gu Mi11, Hong Wang11, Erik Rasmussen12, David Ferry12, Bo H Chao12, Luis Paz-Ares13. 1. Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut. Electronic address: Roy.Herbst@yale.edu. 2. Drug Development Unit, Sarah Cannon Research Institute United Kingdom, London, United Kingdom; Cancer Institute, University College London, London, United Kingdom. 3. Drug Development Unit, Tennessee Oncology/Sarah Cannon Research Institute, Nashville, Tennessee. 4. Tennessee Oncology/Sarah Cannon Research Institute, Chattanooga, Tennessee. 5. NCT/UCC-ECTU, Medical Faculty Carl Gustav Carus, Technical University, Dresden, Germany. 6. Florida Cancer Specialists/Sarah Cannon Research Institute, Englewood, Florida. 7. Centre Oscar Lambret, Lille University, Lille, France. 8. Department of Medicine, University of Washington, Seattle, Washington. 9. Department of Thoracic Oncology, Thoraxklinik Heidelberg, Heidelberg, Germany. 10. Department of Medicine, Royal Marsden Hospital, London and Surrey, United Kingdom. 11. Eli Lilly and Company, Indianapolis, Indiana. 12. Eli Lilly and Company, New York, New York. 13. CNIO-H12o Lung Cancer Unit, Hospital Universitario 12 de Octubre, Universidad Complutense & CIBERONC, Madrid, Spain.
Abstract
INTRODUCTION: Data of first-line ramucirumab plus pembrolizumab treatment of programmed death-ligand 1 (PD-L1)-positive NSCLC (cohort E) are reported (NCT02443324). METHODS: In this multicenter, open-label phase 1a/b trial, patients received ramucirumab 10 mg/kg and pembrolizumab 200 mg every 21 days for up to 35 cycles. PD-L1 positivity was defined as tumor proportion score (TPS) greater than or equal to 1%. Exploratory NanoString biomarker analyses included three T-cell signatures (T-cell-inflamed, Gajewski, and effector T cells) and CD274 gene expression. RESULTS: Cohort E included 26 patients. Treatment-related adverse events of any grade occurred in 22 patients (84.6%). Treatment-related adverse events of grade greater than or equal to 3 were reported in 11 patients (42.3%); the most frequent was hypertension (n = 4, 15.4%). Objective response rate was 42.3% in the treated population and 56.3% and 22.2% for patients with high (TPS ≥ 50%) and lower levels (TPS 1%-49%) of PD-L1 expression, respectively. Median progression-free survival (PFS) in the treated population was 9.3 months, and 12-month and 18-month PFS rates were 45% each. Median PFS was not reached in patients with PD-L1 TPS greater than or equal to 50% and was 4.2 months in patients with PD-L1 TPS 1% to 49%. Median overall survival was not reached in the treated population, and 12-month and 18-month overall survival rates were 73% and 64%, respectively. Biomarker data suggested a positive association among clinical response, three T-cell signatures, CD274 gene expression, and PD-L1 immunohistochemistry. CONCLUSIONS: First-line therapy with ramucirumab plus pembrolizumab has a manageable safety profile in patients with NSCLC, and the efficacy signal seems to be strongest in tumors with high PD-L1 expression.
INTRODUCTION: Data of first-line ramucirumab plus pembrolizumab treatment of programmed death-ligand 1 (PD-L1)-positive NSCLC (cohort E) are reported (NCT02443324). METHODS: In this multicenter, open-label phase 1a/b trial, patients received ramucirumab 10 mg/kg and pembrolizumab 200 mg every 21 days for up to 35 cycles. PD-L1 positivity was defined as tumor proportion score (TPS) greater than or equal to 1%. Exploratory NanoString biomarker analyses included three T-cell signatures (T-cell-inflamed, Gajewski, and effector T cells) and CD274 gene expression. RESULTS: Cohort E included 26 patients. Treatment-related adverse events of any grade occurred in 22 patients (84.6%). Treatment-related adverse events of grade greater than or equal to 3 were reported in 11 patients (42.3%); the most frequent was hypertension (n = 4, 15.4%). Objective response rate was 42.3% in the treated population and 56.3% and 22.2% for patients with high (TPS ≥ 50%) and lower levels (TPS 1%-49%) of PD-L1 expression, respectively. Median progression-free survival (PFS) in the treated population was 9.3 months, and 12-month and 18-month PFS rates were 45% each. Median PFS was not reached in patients with PD-L1 TPS greater than or equal to 50% and was 4.2 months in patients with PD-L1 TPS 1% to 49%. Median overall survival was not reached in the treated population, and 12-month and 18-month overall survival rates were 73% and 64%, respectively. Biomarker data suggested a positive association among clinical response, three T-cell signatures, CD274 gene expression, and PD-L1 immunohistochemistry. CONCLUSIONS: First-line therapy with ramucirumab plus pembrolizumab has a manageable safety profile in patients with NSCLC, and the efficacy signal seems to be strongest in tumors with high PD-L1 expression.
Authors: Karen L Reckamp; Mary W Redman; Konstantin H Dragnev; Katherine Minichiello; Liza C Villaruz; Bryan Faller; Tareq Al Baghdadi; Susan Hines; Leah Everhart; Louise Highleyman; Vassiliki Papadimitrakopoulou; Saiama N Waqar; Jyoti D Patel; Jhanelle E Gray; David R Gandara; Karen Kelly; Roy S Herbst Journal: J Clin Oncol Date: 2022-06-03 Impact factor: 50.717
Authors: Menghuan Guo; Zhiyuan Liu; Jing Si; Jinhua Zhang; Jin Zhao; Zhong Guo; Yi Xie; Hong Zhang; Lu Gan Journal: Biomed Res Int Date: 2021-03-29 Impact factor: 3.411