Phase III ORIENT-12 Trial of TYVYT® (Sintilimab Injection) Combined with Gemzar® (Gemcitabine) and Platinum Chemotherapy Meets Primary Endpoint in First-Line Treatment of Squamous Non-Small Cell Lung Cancer

Suzhou, China, May 7, 2020 /PRNewswire/ -- Innovent Biologics (HKEX stock code: 01801), a biopharmaceutical company dedicated to the research, development, manufacturing, and commercialization of innovative drugs for the treatment of major diseases such as cancer, autoimmune disorders, and metabolic diseases, today jointly announced with Eli Lilly and Company (NYSE ticker: LLY): The innovative PD-1 inhibitor Tyvyt, co-developed by both parties^®(Sintilimab Injection) A Randomized, Double-Blind, Phase III Controlled Clinical Study (ORIENT-12) — Tyvyt^®(Sintilimab Injection, hereinafter referred to as Sintilimab) in combination with Gemzar^®(Gemcitabine for Injection, hereinafter referred to as gemcitabine) and platinum-based chemotherapy met the primary endpoint as first-line treatment for advanced or metastatic squamous non-small cell lung cancer (NSCLC). This is the first global study evaluating a PD-1 antibody in combination with Gemzar^®A Randomized, Double-Blind, Phase III Clinical Study of (Gemcitabine) and Platinum-Based Regimens for First-Line Treatment of Squamous NSCLC.

The study demonstrated that sintilimab in combination with gemcitabine and platinum significantly prolonged progression-free survival (PFS) compared with placebo plus gemcitabine and platinum, meeting the prespecified study endpoint. The significant PFS benefit was observed, and the safety profile was consistent with previously reported findings for sintilimab, with no new safety signals identified. Detailed study results will be presented at upcoming academic conferences.

Innovent and Eli Lilly plan to communicate with the Center for Drug Evaluation (CDE) of the National Medical Products Administration regarding the submission of a new indication application for the first-line treatment of squamous NSCLC with sintilimab in combination with gemcitabine and platinum.

Professor Zhou Caicun, Director of the Department of Oncology at Shanghai Pulmonary Hospital, stated: “Lung cancer ranks first among all cancer-related causes of death (25.2%), with non-small cell lung cancer (NSCLC) accounting for approximately 80% to 85% of cases. About 35% of NSCLC cases are squamous NSCLC. Over the past two decades, advances in pharmacotherapy for NSCLC have primarily focused on non-squamous NSCLC, while drug development for squamous NSCLC has progressed more slowly due to the lack of driver genes and its distinct tumor biological characteristics. The emergence of anti-PD-1 antibodies has introduced a new treatment option for this patient population. We have observed that the study of sintilimab met its prespecified primary endpoint. Compared with pembrolizumab’s KEYNOTE-407 trial, the ORIENT-12 study employed a different combination chemotherapy regimen and is the first randomized controlled trial globally to demonstrate that PD-1 antibody combined with gemcitabine and platinum significantly improves progression-free survival in patients with first-line squamous NSCLC.”

Dr. Hui Zhou, Vice President of the Medical Science and Strategic Oncology Department at Innovent Biologics Group, stated, “Currently, sintilimab is the only anti-PD-1 monoclonal antibody included in the National Reimbursement Drug List. It was approved by the National Medical Products Administration in 2018 for the treatment of relapsed or refractory classical Hodgkin’s lymphoma in patients who have received at least two lines of systemic chemotherapy. We are currently conducting multiple Phase III randomized controlled trials of sintilimab in lung cancer. The results from the ORIENT-12 study are encouraging, and we anticipate that sintilimab has the potential to benefit a broader population of lung cancer patients. This marks the second successful randomized controlled trial in lung cancer for Innovent Biologics, following the achievement of the primary endpoint in the ORIENT-11 study (a randomized, double-blind, Phase III study in first-line non-squamous NSCLC, NCT03607539).”

Dr. Li Wang, Senior Vice President of Eli Lilly China and Head of the Drug Development and Medical Affairs Center, stated, “Not long ago, the Center for Drug Evaluation (CDE) of the National Medical Products Administration accepted the new indication application for sintilimab as a first-line treatment for non-squamous non-small cell lung cancer (nsqNSCLC). The exciting results from the ORIENT-12 study further demonstrate the potential of sintilimab in the treatment of squamous non-small cell lung cancer. We would like to express our gratitude to all the participating patients and their families, investigators, clinical trial centers, and our colleagues at Innovent Bio. We look forward to bringing this novel therapeutic option to lung cancer patients in China as soon as possible.”

AboutORIENT-12 Study

The ORIENT-12 study is an evaluation of Tyvyt^®(Sintilimab) or placebo in combination with Gemzar^®A Randomized, Double-Blind, Phase III Controlled Clinical Study on the Efficacy and Safety of (Gemcitabine) and Platinum-Based Regimens as First-Line Treatment for Advanced or Metastatic Squamous NSCLC (ClinicalTrials.gov, NCT03629925). The primary endpoint was progression-free survival (PFS) assessed by an Independent Radiology Review Committee (IRRC) according to RECIST v1.1 criteria. Secondary endpoints included overall survival (OS), safety, and others.

A total of 357 subjects were enrolled in this study and randomized in a 1:1 ratio to receive Tyvyt^®(Sintilimab Injection) 200 mg or placebo in combination with Gemzar^®(Gemcitabine for Injection) and platinum-based therapy, administered once every 3 weeks; after completing 4 or 6 cycles of combination therapy, proceed to Tyvyt^®(Sintilimab Injection) or placebo maintenance treatment until disease progression, intolerable toxicity, or other circumstances requiring treatment discontinuation. Patients in the control group may conditionally cross over to Tyvyt upon disease progression.^®(Sintilimab Injection) Monotherapy.

On Squamous Non-Small Cell Lung Cancer(sqNSCLC)

Lung cancer is currently the most prevalent malignant tumor in China, ranking first in both incidence and mortality. Non-small cell lung cancer (NSCLC) accounts for approximately 80% to 85% of all lung cancer cases. About 70% of NSCLC patients are diagnosed with locally advanced or metastatic disease that is not amenable to curative surgery. Furthermore, a significant proportion of early-stage NSCLC patients who undergo surgical treatment experience recurrence or distant metastasis, ultimately leading to death due to disease progression. Approximately 35% of NSCLC patients in China have squamous NSCLC. Squamous NSCLC typically lacks driver genes, and the response rate to first-line chemotherapy is around 30%. Currently, only pembrolizumab in combination with carboplatin and paclitaxel has been approved by the U.S. Food and Drug Administration (FDA) and the National Medical Products Administration (NMPA) for this patient population. Treatment options remain limited, indicating a substantial unmet medical need.

About Tyvyt^®(Sintilimab Injection)

Tyvyt^®(Sintilimab Injection) is an innovative, international-quality biologic drug jointly developed by Innovent Biologics and Eli Lilly and Company in China. Its first approved indication was for relapsed/refractory classical Hodgkin lymphoma, and it was included in the 2019 Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Lymphoma. In April 2020, the National Medical Products Administration (NMPA) officially accepted the application for Tyvyt.^®(Sintilimab Injection) Application for the indication of first-line treatment of non-squamous non-small cell lung cancer (nsqNSCLC). During the 2019 National Reimbursement Drug List negotiations, Tyvyt^®(Sintilimab Injection) is the only PD-1 inhibitor included in the National Reimbursement Drug List.

Tyvyt®^®(Sintilimab Injection) is a human immunoglobulin G4 (IgG4) monoclonal antibody that specifically binds to the PD-1 molecule on the surface of T cells, thereby blocking the PD-1/Programmed Death-Ligand 1 (PD-L1) pathway responsible for tumor immune tolerance. This action reactivates the anti-tumor activity of lymphocytes, achieving the goal of cancer treatment. Currently, more than twenty clinical studies (including over ten registrational clinical trials) are underway to investigate the anti-tumor effects of sintilimab in other solid tumors. Innovent Bio is also conducting global clinical research on Sintilimab Injection.

About Innovent Bio

“Rooted in Trust, Realized through Action.” Innovent Bio’s vision and goal is to develop high-quality biologics that are affordable for the general public. Established in 2011, Innovent Bio is dedicated to the development, manufacturing, and commercialization of innovative medicines for the treatment of major diseases, including cancer, autoimmune disorders, and metabolic diseases. On October 31, 2018, Innovent Biologics was listed on the Main Board of The Stock Exchange of Hong Kong Limited, with stock code: 01801.

Since its establishment, the company has stood out among numerous biopharmaceutical companies with its innovative achievements and internationalized operational model. It has established a product pipeline comprising 23 new drug candidates, covering multiple therapeutic areas including oncology, autoimmune diseases, and metabolic disorders. Among these, six candidates have been selected for the National “Major New Drug Development” Special Program, 16 have entered clinical studies, five have advanced to Phase III or pivotal registration clinical trials, and marketing applications for four monoclonal antibody products have been accepted by the National Medical Products Administration (NMPA), all of which have been included in the priority review program. One product (Sintilimab Injection, brand name: Tyvyt^®, English trademark: TYVYT^®) received marketing approval from the National Medical Products Administration, with its first approved indication being relapsed/refractory classical Hodgkin lymphoma, and in November 2019 became the only PD-1 inhibitor included in the updated National Reimbursement Drug List.

Innovent Bio has assembled a high-caliber team for the development and industrialization of biopharmaceuticals, featuring international advanced expertise and numerous returnee experts. The company has established strategic collaborations with global pharmaceutical leaders, including Eli Lilly and Company, Adimab, Incyte, and Hanmi Pharmaceutical. Innovent Bio is committed to working collaboratively to elevate the development of China’s biopharmaceutical industry, thereby enhancing medication accessibility and fulfilling the public’s aspiration for better health and well-being. For more details, please visit the company website:www.innoventbio.com。

About Eli Lilly and Company

Eli Lilly and Company is a global leading pharmaceutical company dedicated to improving human health through innovation. Founded more than a century ago, the company’s founder was committed to producing high-quality medicines to meet tangible medical needs. Today, we remain steadfast in this mission and guide our work by it. Worldwide, our employees strive to discover and develop medicines that can transform lives and deliver them to patients who truly need them. Furthermore, we are committed to enhancing public understanding of diseases and improving disease management, while giving back to society through charitable initiatives and volunteer activities. For more information about Eli Lilly and Company, please visit:www.lilly.com。

Strategic Cooperation between Innovent Bio and Eli Lilly

Innovent Bio and Eli Lilly and Company entered into a biopharmaceutical drug development collaboration in March 2015, which remains one of the largest partnerships to date between a Chinese biopharmaceutical company and a multinational pharmaceutical corporation. Under the terms of the agreement, Innovent Bio and Eli Lilly and Company will jointly develop and commercialize in China, including Tyvyt^®Oncology drugs, including sintilimab injection. In October 2015, the two parties announced a further expansion of their established drug development collaboration, adding three novel oncology therapeutic antibodies. In August 2019, the collaboration was extended to the field of diabetes, with Innovent Bio licensed to develop and commercialize in China a potential global best-in-class novel clinical-stage diabetes drug from Eli Lilly. These three collaborations with Eli Lilly and Company mark that Innovent Bio has established a comprehensive strategic partnership between a Chinese innovative pharmaceutical company and a global pharmaceutical giant, covering new drug research and development, clinical studies, manufacturing quality, and marketing and sales.

Declaration:

1. This indication is an investigational use of the drug and has not yet been approved in China.