AKESO (09926): The HARMONi-6 study comparing the first-line treatment of late-stage sq-NSCLC with the combination of Ivoxi and chemoradiotherapy versus combination of Tislelizumab and chemoradiotherapy will be published in the prestigious medical journal The Lancet & 2025 ESMO.

AKESO (09926) announced that the research results of HARMONi-6 / AK112-306 conducted by Professor Lu Shun, Director of Oncology Department at Shanghai Chest Hospital, were released at the 2025 European Society for Medical Oncology (ESMO) Presidential Forum and simultaneously published in the leading international medical journal, THE LANCET. HARMONi-6 / AK112-306 (CTR20231272 / NCT 05840016) is a randomized, controlled, multicenter Phase III clinical study evaluating the combination of evofosfamide and chemotherapy versus topotecan and chemotherapy as first-line treatment for advanced sq-NSCLC. The main endpoint of this study is Progression-Free Survival (PFS) evaluated by IRCC based on RECIST v1.1, with Overall Survival (OS) as a key secondary endpoint. The HARMONi-6 study included 532 subjects, with baseline balance between the two groups, and 92.3% of subjects were in clinical stage IV. The distribution of squamous cell carcinoma characteristics in the study population was consistent with the real-world patient population, with a central type squamous cell carcinoma proportion of approximately 63%. PD-L1 expression levels also matched clinical reality. The trial results showed: The combination of evofosfamide and chemotherapy compared to topotecan and chemotherapy achieved the primary endpoint of PFS, with a decisive positive outcome, significant statistical benefit, and significant clinical benefit. The evofosfamide group significantly prolonged patients' PFS compared to the control group. The intergroup PFS HR of evofosfamide and chemotherapy compared to topotecan and chemotherapy was 0.60, p <0.0001. The median PFS in the evofosfamide group was 11.14 months, compared to 6.9 months in the control group. The HARMONi-6 study showed an absolute improvement in PFS between the two groups of PFS = 4.24 months. In all subgroups, the combination of evofosfamide and chemotherapy showed significant benefits compared to topotecan and chemotherapy, regardless of PD-L1 expression levels (positive or negative), liver metastasis status, or the number of baseline metastatic sites. In the PD-L1 negative (TPS <1%) population, the median PFS was 9.9 months vs. 5.7 months, with a PFS HR of 0.55. In the PD-L1 positive (TPS 1%) population, the median PFS was 12.6 months vs. 8.6 months, with a PFS HR of 0.66. For patients with liver metastasis, the PFS HR was 0.53, and for those without liver metastasis, the PFS HR was 0.64. The PFS HR for patients with 3 baseline metastatic sites was 0.46, and for those with <3 sites, it was 0.64. The overall safety of the evofosfamide combination chemotherapy was good, with no new safety signals identified. The rates of treatment-related serious adverse events and grade 3 or higher bleeding events were similar to the control group. The new indication application for evofosfamide combination chemotherapy as first-line treatment for sq-NSCLC has been accepted by the Center for Drug Evaluation (CDE) and is under review, providing hope for more patients. The results of this clinical study demonstrate the breakthrough clinical value of the evofosfamide combination chemotherapy regimen compared to the PD-1 combination chemotherapy regimen, filling a clinical gap in the treatment of sq-NSCLC with anti-angiogenic drug bevacizumab. This once again demonstrates the excellent efficacy and safety of the evofosfamide treatment and solidifies its global leadership position.