This is the seventh NMPA-approved indication of TYVYT® (sintilimab injection). The first six indications of TYVYT® (sintilimab injection) are included in the National Reimbursement Drug List (NRDL), making TYVYT® (sintilimab injection) the only PD-1 inhibitor for the first-line treatment of five high-incidence cancer types in the NRDL – including non-squamous NSCLC, squamous NSCLC, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer. TYVYT® (sintilimab injection) is also the first and the only immunotherapy medicine for gastric cancer in the NRDL. This is also the eighth NMPA-approved indication of BYVASDA® (bevacizumab injection).

This new approval in China was based on the results of a randomized, double-blind, multi-center, prospective Phase 3 clinical trial (ORIENT-31, NCT03802240) evaluating TYVYT® (sintilimab injection) ± BYVASDA® (bevacizumab injection) + chemotherapy (pemetrexed and cisplatin) for the treatment of patients with EGFR-mutated non-squamous NSCLC who progressed after EGFR-TKI therapy.

In the second interim analysis (data cutoff date: March 31^st, 2022), in the intent-to-treat (ITT) population, based on the assessment by the Independent Radiographic Review Committee (IRRC), significant and clinically meaningful PFS benefit was sustained with sintilimab plus bevacizumab plus chemotherapy compared with chemotherapy alone (median PFS: 7.2 months vs. 4.3 months; HR=0.51, p<0.0001). Additionally, the key secondary endpoints of objective response rate (ORR) and duration of response (DOR) were improved with sintilimab plus bevacizumab plus chemotherapy, compared with chemotherapy alone.

As of data cutoff date July 4^th, 2022, a trend towards overall survival (OS) benefit with sintilimab plus bevacizumab and chemotherapy was observed although the median OS for chemotherapy was prolonged due to crossover after progression in chemotherapy group. The median OS for sintilimab plus bevacizumab plus chemotherapy and chemotherapy alone were 21.1 months vs 19.2 months, HR=0.98. After adjusting for crossover, the OS HR ranged from 0.79 to 0.84. In the exploratory analyses of quality of life, compared with the chemotherapy alone, sintilimab plus bevacizumab and chemotherapy showed longer median time-to-deterioration of the Global Health Status Dimension Score of EORTC Quality of Life Questionnaire Core 30 (QLQ-C30). The safety profile of this study was consistent with that observed in previously reported studies of sintilimab and bevacizumab, without new or unexpected safety signals.

The first interim analysis results of ORIENT-31 were published in The Lancet Oncology on July 28, 2022^[i]. The second interim analysis results were published in The Lancet Respiratory Medicine on May 5, 2023^[ii].

The principal investigator of the ORIENT-31 Study, Prof. Shun Lu from the Oncology Department of Shanghai Chest Hospital, stated, "Different from the western population, about half of the Chinese patients with NSCLC have EGFR mutations. EGFR-TKI targeted therapy is the first line treatment choice in NSCLC patients with EGFR sensitive mutation. However, almost all patients will eventually develop TKI-resistance and progression of disease and there are no good treatment options for EGFR-TKI failed NSCLC population^[iii]. The ORIENT-31 study is globally the first prospective, randomized and double-blind Phase 3 study that demonstrated that PD-1 inhibitor ± bevacizumab combined with chemotherapy can significantly prolong PFS in EGFR-mutant non-squamous NSCLC population who have failed EGFR-TKI treatment. In addition, compared with standard platinum-based chemotherapy, sintilimab and bevacizumab combined with chemotherapy improved the ORR and DOR, showing survival benefit trend as well as improvement in quality of life. The approval of this indication brings a new treatment option for EGFR-mutated non-squamous NSCLC patients who have failed EGFR-TKI treatment, benefiting more Chinese patients."

Dr. Michael Yu, Founder, Chairman and CEO of Innovent, stated, "Despite proven efficacy in broad types of cancer, immunotherapy has rarely made breakthroughs in the treatment of driver gene-positive non-squamous NSCLC patients. We are excited about the results of ORIENT-31 study and this new approval marks the first immunotherapy combination therapy approved for patients with driver gene-positive non-squamous NSCLC in China, and making TYVYT® the first PD-1 inhibitor approved for driver gene-positive non-squamous NSCLC globally. Innovent will continue our commitment to innovation and contribute to the 'Healthy China 2030' strategy."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "Lung cancer is a malignant tumor with the highest mortality rate and incidence in China, representing a large unmet medical need^[iv]. The new approval of TYVYT® is another important clinical development milestone, bringing new hope to the broader lung cancer patients with EGFR mutation. Innovent will continue to develop more novel therapies to address unmet clinical needs and bring more effective treatment options to patients in China and globally. "

Mr. Ben Basil, President and General Manager of Lilly China, stated, "Since its debut in 2018, TYVYT® has been approved consecutively six indications including lymphoma, lung cancer, liver cancer, esophageal cancer to gastric cancer, and all six indications have been included in the National Reimbursement Drug List (NRDL), benefiting millions of Chinese patients. I am very excited to see another indication approved today, bringing a brand new treatment option to NSCLC patients who have failed EGFR-TKI treatment in China. TYVYT® sets a great example for our partnership with Innovent. We will continually work with our local partners in bringing more innovative drugs to Chinese patients, continuously making contributions to the 'Healthy China 2030' blueprint."

Dr. Li Wang, Lilly Corporate Senior Vice President, Head of China Drug Development & Medical Affairs Center, stated, "The ORIENT-31 study is globally the first study in immunotherapy to confirm benefits in EGFR positive lung cancer patients who have failed EGFR-TKI treatment. The two interim analyses have demonstrated encouraging clinical results, breaking the dilemma of EGFR-TKI resistance. With the newly approved indication, TYVYT® provides a new treatment option and brings new hope to patients with EGFR-mutated non-squamous NSCLC who progressed after EGFR-TKI therapy in China."