Akeso (09926) announced that the results of the HARMONi-6 / AK112 – 306 study were prominently presented by Professor Lu Shun, Director of Oncology at Shanghai Chest Hospital, at the 2025 European Society for Medical Oncology (ESMO) plenary session and simultaneously published in the prestigious medical journal, The Lancet. HARMONi-6 / AK112 – 306 (CTR20231272 / NCT 05840016) is a randomized, controlled, multicenter Phase III clinical trial evaluating the efficacy of Ivosidenib combined with chemotherapy versus Tezolizumab combined with chemotherapy as first-line treatment for advanced sq-NSCLC. The primary endpoint of the study was progression-free survival (PFS) assessed by independent radiology review committee (IRRC) based on RECIST v1.1, with overall survival (OS) as a key secondary endpoint. A total of 532 subjects were enrolled in the HARMONi-6 study, with balanced baseline characteristics; 92.3% of the participants were classified as Stage IV. The characteristics of squamous cell carcinoma were consistent with clinical practice, with approximately 63% being centrally located squamous cell carcinoma, aligning with the real-world patient distribution, and PD-L1 expression levels reflecting clinical realities. The study results demonstrated that Ivosidenib combined chemotherapy met the primary endpoint for PFS, achieving a decisive positive outcome with significant statistical and clinical benefits, substantially prolonging PFS for patients in the Ivosidenib group compared to the control group. The PFS hazard ratio (HR) for the Ivosidenib versus Tezolizumab combination was 0.60, p<0.0001. The median PFS (m PFS) in the Ivosidenib group was 11.14 months, while the control group had an m PFS of 6.9 months. The HARMONi-6 study achieved an absolute improvement in intergroup PFS of △PFS = 4.24 months across various subgroups, indicating significant benefits of Ivosidenib combined chemotherapy over Tezolizumab combined chemotherapy, irrespective of PD-L1 expression level (whether PD-L1 positive or negative), the presence of liver metastases, or the number of metastatic sites at baseline. In the PD-L1 negative (TPS ≤ 1%) population, the m PFS was 9.9 months versus 5.7 months, with a PFS HR of 0.55 (95% CI: 0.37, 0.82). In the PD-L1 positive (TPS ≥ 1%) group, the m PFS was 12.6 months versus 8.6 months, with a PFS HR of 0.66 (95% CI: 0.46, 0.95). For patients with liver metastases, the PFS HR was 0.53; in those without liver metastases, the HR was 0.64. Among patients with three or more metastatic sites at baseline, the PFS HR was 0.46; those with fewer than three sites had a PFS HR of 0.64. The Ivosidenib group exhibited good overall safety without new safety signals observed. The incidence of treatment-related serious adverse events and grade 3 or higher bleeding events was similar to that of the control group. The new application for Ivosidenib combination chemotherapy as first-line treatment for sq-NSCLC has been accepted by CDE and is under review, offering hope for more patients. The results of this clinical study demonstrate the groundbreaking clinical value of Ivosidenib combination chemotherapy compared to PD-1 combination therapy, filling a clinical gap left by the anti-angiogenic agent Bevacizumab in the treatment of sq-NSCLC, and once again showcasing the superior efficacy and safety of the Ivosidenib regimen, solidifying its global leadership. HARMONi-6 / AK112 – 306 (CTR20231272 / NCT 05840016) is a randomized, controlled, multicenter Phase III clinical study evaluating the efficacy of Ivosidenib combined with chemotherapy versus Tezolizumab combined with chemotherapy as first-line treatment for advanced sq-NSCLC. The primary endpoint for the study is PFS as assessed by IRRC based on RECIST v1.1, and the key secondary endpoint is OS. A total of 532 subjects were enrolled in the HARMONi-6 study, with balanced baseline characteristics; 92.3% of the participants were classified as Stage IV. The characteristics of squamous cell carcinoma were consistent with clinical practice, with approximately 63% being centrally located squamous cell carcinoma, and the PD-L1 expression levels aligning with clinical realities. For more significant stock information in Hong Kong, download the Zhitong Finance app for more Hong Kong stock and overseas investment insights, please click www.zhitongcaijing.com (search “Zhitong Finance”); to join the Zhitong Hong Kong stock investment group, please add Zhitong customer service WeChat (ztcjkf).