On August 5, 2021 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), 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 (NYSE: LLY) reported 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 (Press release, Innovent Biologics, AUG 5, 2021, View Source [SID1234586030]). In addition, biomarker results from the trial provide important insights for patients with high major histocompatibility complex (MHC) class-II expression. These findings were published today in the Journal of Thoracic Oncology. (https://www.sciencedirect.com/science/article/pii/S1556086421023303)
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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 tumor microenvironment is helping scientists find suitable biomarkers as potential targets for cancer treatment. These ORIENT-11 biomarker results published in the Journal of Thoracic Oncology will help us further understand the mechanism of action of this immunotherapy-based combination in order to identify patients who are more likely to respond to treatment."
About the ORIENT-11 Trial
ORIENT-11 is a randomized, double-blind, Phase 3 clinical trial evaluating the efficacy and safety of sintilimab or placebo in combination with pemetrexed and platinum chemotherapy as a first-line treatment for advanced or recurrent non-squamous non-small cell lung cancer (nsqNSCLC) without sensitizing EGFR mutations or ALK rearrangements (ClinicalTrials.gov, NCT03607539). The primary endpoint is progression-free survival (PFS) assessed by Independent Radiographic Review Committee based on RECIST v1.1. The key secondary endpoints include overall survival (OS) and safety profile.
A total of 397 subjects have been enrolled in the ORIENT-11 trial and randomized in a 2:1 ratio to receive either sintilimab 200mg or placebo in combination with pemetrexed and platinum chemotherapy every three weeks for up to four cycles, followed by either sintilimab injection or placebo plus pemetrexed maintenance therapy. The subjects will receive treatment until radiographic disease progression, unacceptable toxicity or any other conditions that require treatment discontinuation. Conditional crossover is permitted.
About Lung Cancer
Globally, lung cancer is the leading cause of cancer death, killing nearly 1.8 million people worldwide each year. In the U.S., lung cancer is the second most common cancer (not counting skin cancer) and the leading cause of cancer death, responsible for nearly 25 percent of all cancer deaths – more than those from colorectal, breast and prostate cancers combined. Non-small cell lung cancer (NSCLC) accounts for approximately 85 percent of all lung cancers, and about 70 percent of those with NSCLC have the nonsquamous subtype. Fifty percent of NSCLC patients present with advanced or metastatic disease at diagnosis.
About Sintilimab
Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.
In China, sintilimab has been approved for four indications, including:
The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma
Additionally, Innovent currently has a regulatory submission under review in China for sintilimab for the second-line treatment of squamous non-small cell lung cancer.
Innovent also has two clinical studies of sintilimab that have met their primary endpoints:
In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma
The second-line treatment of esophageal squamous cell carcinoma
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.
Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.