On May 7, 2023 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, ophthalmology and other major diseases, reported that second interim analysis and survival analysis results of the ORIENT-31 study (NCT03802240) have been published in the Lancet Respiratory Medicine (https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00135-2/fulltext) (Press release, Innovent Biologics, MAY 7, 2023, View Source [SID1234631111]). This randomized, double-blinded, multi-center Phase 3 study evaluated TYVYT(sintilimab) with or without anti-VEGF antibody therapy (BYVASDA [bevacizumab injection]) combined with chemotherapy (pemetrexed and cisplatin) in patients with EGFR-mutated non-squamous non-small cell lung-cancer (NSCLC) who progressed after EGFR-TKI therapy. The first interim analysis has been published in the Lancet Oncology in 2022i.
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In the second interim analysis (data cutoff date: March 31th, 2022), the main purpose is to analyze the median progression-free survival (mPFS) of the preset sintilimab plus chemotherapy group (Arm B) versus chemotherapy group (Arm C) in the intent-to-treat (ITT) population, update the results of sintilimab plus bevacizumab plus chemotherapy group (Arm A) and report the overall survival results of the study for the first time. The median follow-up duration of progression-free survival (PFS) were 12.9 months, 15.1 months, and 14.4 months in Arm A, Arm B and Arm C, respectively. Based on the assessment by the Independent Radiographic Review Committee (IRRC), the median PFS were 7.2 months (95%CI: 6.6, 9.3) in Arm A, 5.5 months (95%CI: 4.5, 6.1) in Arm B, and 4.3 months (95%CI: 4.1, 5.3) in Arm C. Arm B demonstrated a statistically significant and clinically meaningful improvement in PFS compared to Arm C, with a HR of 0.72 (95%CI: 0.55, 0.94, P=0.016), which reached pre-specified superiority boundary value. Significant PFS benefit was sustained in Arm A compared to Arm C with a HR of 0.51 (95%CI: 0.39, 0.67, p<0.0001).
As of data cutoff July 4th, 2022, a trend towards overall survival (OS) benefit with Arm A was observed although the median OS for Arm C was prolonged due to crossover after progression in Arm C. The median OS for Arm A and Arm C 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, Arm A showed longer median time-to-deterioration of the Global Health Status Dimension Score of EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) compared with Arm C.
The safety results were generally consistent with those in the first interim analysis; in particular, treatment-related adverse events of grade ≥3 were 56% in Arm A, 41% in Arm B and 49% in Arm C. 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.
Globally, ORIENT-31 is the first multi-center, double-blind, prospective Phase 3 study to demonstrate significant PFS benefit of combination therapy of an anti-PD-1 antibody with chemotherapy in patients with EGFR mutated nsqNSCLC that progressed on prior EGFR-TKI therapy. Sintilimab and chemotherapy group showed significant improved PFS with an optimal safety profile. With the extension of follow-up time, sintilimab plus bevacizumab and chemotherapy group continued to show a durable, clinically meaningful PFS benefit.
The principal investigator of the ORIENT-31 Study, Prof. Shun Lu from the Oncology Department of Shanghai Chest Hospital, stated, " ORIENT-31 is globally the first prospective, randomized, double-blind Phase 3 study that demonstrated significant PFS benefit of combination therapy of anti-PD-1 antibody and chemotherapy with or without bevacizumab in patients with EGFR mutated non-squamous NSCLC that progressed on prior EGFR-TKI therapy, which was revolutionary in immunotherapy. I am pleased to witness the first and second interim analysis results of the ORIENT-31 study were published in international authoritative and influential journals. Besides, I hope that the recent approval of sintilimab in combination with bevacizumab and chemotherapy in treatment of patients with EGFR mutated non-squamous NSCLC that progressed on prior EGFR-TKI therapy can bring a new treatment option benefiting more cancer patients."
Dr. Hui Zhou, Senior Vice President of Innovent, stated, "the ORIENT-31 study is the first Phase 3 study that met primary endpoints in the world evaluating efficacy of PD-1 inhibitor and chemotherapy with or without bevacizumab in patients with EGFR mutated non-squamous NSCLC that progressed on prior EGFR-TKI therapy. The results of first and second interim analysis were published in the Lancet Oncology and the Lancet Respiratory Medicine, respectively. That represents the international academia’s recognition of high quality, innovative clinical trial conducted by investigators in China, and is also a milestone marking Innovent’s solid and outstanding capabilities in new drug development. Meanwhile, we look forward to the approval of sintilimab in combination with bevacizumab and chemotherapy based on the results of the ORIENT-31 study can bring new hope to patients with EGFR mutated non-squamous NSCLC that progressed on prior EGFR-TKI therapy. Innovent endeavors to advance innovative drug development targeting unmet medical needs, to bring more effective and affordable treatment options to patients in China and the world."