On August 8, 2020 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, reported with Eli Lilly and Company ("Lilly",NYSE: LLY) that interim analysis data from ORIENT-11 were released today in an oral presentation at the IASLC World Conference on Lung Cancer (WCLC) 2020 Virtual Presidential Symposium. On the same day, the data was published online by the Journal of Thoracic Oncology. This trial was conducted to assess the efficacy of TYVYT (sintilimab injection) in combination with ALIMTA (pemetrexed) and platinum chemotherapy as a first-line treatment in people with nonsquamous non-small cell lung cancer (nsqNSCLC) without sensitive EGFR mutation or ALK rearrangement.
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ORIENT-11 is a randomized, double-blind, Phase 3 clinical trial evaluating TYVYT (sintilimab injection) or placebo in combination with ALIMTA (pemetrexed) and platinum chemotherapy as a first-line treatment for advanced or recurrent nsqNSCLC without sensitizing EGFR mutations or ALK rearrangements. Based on the interim analysis conducted by the Independent Data Monitoring Committee (IDMC), TYVYT (sintilimab injection) in combination with ALIMTA (pemetrexed) and platinum chemotherapy demonstrated a statistically significant improvement in progression-free survival (PFS) compared with placebo in combination with ALIMTA (pemetrexed) and platinum chemotherapy, which met the pre-defined efficacy criteria. After a median follow up of 8.9 months, the median PFS of the sintilimab combination and the placebo combination assessed by the Independent Radiographic Review Committee (IRRC) was 8.9 months and 5.0 months, respectively [HR (95%CI) = 0.482 (0.362, 0.643), P < 0.00001]. The median overall survival (OS) was not reached in both groups, but OS showed an improvement favoring the sintilimab combination (HR=0.609, 95%CI: 0.400-0.926). Confirmed objective response rate (assessed by IRRC) was improved from 29.8% to 51.9%, and the sintilimab combination showed a shorter time to response (median time to response: 1.51 months in the sintilimab combination versus 2.63 months in the placebo combination). The safety profile was consistent with previously reported sintilimab studies, and no new safety signals were identified. National Medical Products Administration (NMPA) of China has accepted the supplemental New Drug Application (sNDA) for this indication.
Professor Li ZHANG, Head of Department of Internal Medicine, Sun Yat-sen University Cancer Center, the primary investigator of the ORIENT-11 trial, stated: "According to data released by the National Cancer Centre in 2019, lung cancer currently has the highest incidence and mortality of all cancers. Immunotherapy combined with chemotherapy has become one of the standard first-line treatments for patients with negative driver genes. The ORIENT-11 trial has demonstrated a significant delay of disease progression with sintilimab in combination with chemotherapy in this patient population. We are honored to be selected as one of the oral presentations in the Presidential Symposium to share this clinical data."
Dr. Hui ZHOU, Vice President of Medical Science and Strategy Oncology of Innovent, stated: "ORIENT-11 showed a significant improvement in progression-free survival in patients who received sintilimab combined with conventional chemotherapy as a first-line treatment compared with those who received chemotherapy alone. We would like to thank the patients and investigators involved in ORIENT-11 for their important contributions to this landmark trial."
Dr. Li WANG, Senior VP of Lilly China and Head of Lilly China Drug Development and Medical Affairs Center, stated: "Being able to present the results of ORIENT-11 at the WCLC 2020 Presidential Symposium is a major recognition. With these encouraging results of ORIENT-11, sintilimab may soon be able to expand its indication to the first-line treatment of non-squamous NSCLC. We look forward to its potential approval in China, with the goal of helping more patients with lung cancer and giving these patients and their families hope of a longer life."
About ORIENT-11 Trial
ORIENT-11 is a randomized, double-blind, Phase 3 clinical trial evaluating the efficacy and safety of TYVYT (sintilimab injection) or placebo in combination with ALIMTA (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 ALIMTA (pemetrexed) and platinum chemotherapy every 3 weeks for up to 4 cycles, followed by either sintilimab or placebo plus ALIMTA (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 nsqNSCLC
Lung cancer is a malignancy with the highest morbidity and mortality in China. NSCLC accounts for about 80 to 85 percent of lung cancer. Approximately 70 percent of NSCLC is locally advanced or metastatic at initial diagnosis, rendering those patients with no chance of radical resection. Meanwhile, even after radical surgery, patients still have a high chance of recurrence and eventually die from disease progression. About 70 percent of NSCLC in China is the nonsquamous subtype and 50 percent of nsqNSCLC is without sensitizing EGFR mutations or ALK rearrangements. These patients do not respond well to targeted therapy and there are limited treatment options available to them.
About TYVYT (Sintilimab Injection)
TYVYT (sintilimab injection), an innovative drug with global quality standards jointly developed in China by Innovent and Lilly, has been granted marketing approval by the NMPA for the treatment of relapsed or refractory classic Hodgkin’s lymphoma after at least two lines of systemic chemotherapy, and included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. TYVYT (sintilimab injection) is the only PD-1 inhibitor that has been included in the new Catalogue of the National Reimbursement Drug List (NRDL) in November 2019. In April 2020, the NMPA accepted the sNDA for TYVYT (sintilimab injection) in combination with ALIMTA (pemetrexed) and platinum as first-line therapy in non-squamous non-small cell lung cancer (NSCLC). In May 2020, TYVYT (sintilimab injection) combined with Gemzar (gemcitabine for injection) and platinum chemotherapy met the predefined primary endpoint in the Phase 3 ORIENT-12 study as first-line therapy in patients with locally advanced or metastatic squamous NSCLC, and TYVYT (sintilimab injection) monotherapy met the primary endpoint in the ORIENT-2 study as second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma as well.
TYVYT (sintilimab injection) is a type of 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 for sintilimab injection to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials. Meanwhile, we are actively developing it globally.