Innovent Biologics, Inc., a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, and Eli Lilly and Company today announced new and updated data from the ORIENT-11 study demonstrating a sustained survival benefit of sintilimab in combination with pemetrexed and platinum chemotherapy in the first-line treatment of patients with nonsquamous non-small cell lung cancer. In addition, biomarker results from the trial provide important insights for patients with high major histocompatibility complex (MHC) class-II expression.
In August 2020, interim analysis data from ORIENT-11 were released in an oral presentation at the IASLC World Conference on Lung Cancer (WCLC) 2020 Virtual Presidential Symposium. These interim data were simultaneously published online by the Journal of Thoracic Oncology.
ORIENT-11 is a randomized, double-blind Phase 3 clinical trial evaluating sintilimab in combination with pemetrexed and platinum chemotherapy compared to placebo in combination with pemetrexed and platinum chemotherapy as a first-line treatment for locally advanced or metastatic nonsquamous NSCLC without sensitizing EGFR mutations or ALK rearrangements. The Journal of Thoracic Oncology manuscript discloses, as of January 15, 2021, with a median follow-up of 22.9 months, the median overall survival (OS) of patients receiving the sintilimab combination was not yet reached. The sintilimab combination demonstrated a sustainable OS benefit (HR=0.60, 95% CI: 0.45-0.79; p=0.0003), and the median OS for those receiving the placebo combination was 16.8 months.
Whole transcriptome sequencing of baseline tumor samples was performed to probe the predictive and correlative biomarkers, showing that high or medium immune cell infiltration was strongly associated with improved progression-free survival (PFS) in the sintilimab combination group. In particular, high MHC class-II presentation pathway expression was significantly correlated with prolonged PFS (HR=0.32, 95% CI: 0.19-0.54; p<0.0001) and OS (HR=0.36, 95% CI: 0.20-0.64; p=0.0005) in the sintilimab combination group.
Professor Li ZHANG, Head of Department of Internal Medicine, Sun Yat-sen University Cancer Center, the primary investigator of ORIENT-11 and the corresponding author of the manuscript, stated, "Sintilimab in combination with pemetrexed and platinum chemotherapy demonstrated a sustainable survival benefit after long-term follow-up in the ORIENT-11 study. These data showed that this sintilimab combination should be further evaluated as front-line therapy for patients with previously untreated, locally advanced or metastatic nonsquamous non-small cell lung cancer without EGFR or ALK genomic tumor aberrations."
Dr. Wei Xu, Vice President of Translational Medicine of Innovent and co- corresponding author of the manuscript, stated, "Immunotherapy based on PD-1 and PD-L1 antibodies has revolutionized clinical practice of treating non-small cell lung cancer. However, the precise patient population who will benefit from immunotherapy-chemotherapy combination treatment is still unclear. We explored the gene expression profile in the tumor microenvironment and found that the infiltration of antigen-presenting cells and high expression of the MHC-II antigen presentation pathway correlated with improved outcomes in patients who received the sintilimab-pemetrexed-platinum chemotherapy combination. This finding contributes to a better understanding of the mechanism of action of the immunotherapy-chemotherapy combination which could help inform selection of suitable patients for future sintilimab studies. Publication of this study in the Journal of Thoracic Oncology is a recognition of the important work by this research team and we will continue to explore new areas in immuno-oncology, with the goal of identifying additional novel approaches to treat cancer in clinical practice."
Dr. Li WANG, Senior VP of Lilly China and Head of Lilly China Drug Development and Medical Affairs Center, stated: "We're excited to see that the results of ORIENT-11 show sintilimab in combination with pemetrexed and platinum chemotherapy can bring an overall survival benefit to patients with nonsquamous non-small cell lung cancer in the first-line treatment setting. Also, research of the tum...
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