On September 8, 2024 Akeso (9926. HK) reported that its internally developed PD-1/VEGF bispecific antibody ivonescimab showed clinically significant results from a Phase II study, either as a monotherapy or in combination with chemotherapy, for the perioperative treatment of resectable non-small cell lung cancer (NSCLC) at the 25th World Conference on Lung Cancer (WCLC) (Press release, Akeso Biopharma, SEP 8, 2024, View Source [SID1234646408]). This marks ivonescimab’s third oral presentation at an international conference in 2024. Professor Zhao Xiaoliang from Tianjin Medical University Cancer Hospital delivered an oral presentation at WCLC, sharing China’s advancements in innovative cancer immunotherapies with global experts.

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As of February 2024, the AK112-205 study enrolled 60 patients, with 78.3% in stage III and 90% in N+ stage (Among N+ stage patients, 70% are in N2 stage). Of these, 49 underwent surgery (all R0 resections). The study results demonstrated that perioperative ivonescimab monotherapy or combined with chemotherapy for resectable NSCLC demonstrated high rates of pathological complete response (pCR) and major pathological response (MPR) in this phase II study.

Compared with ivonescimab monotherapy, rates of MPR and pCR in ivonescimab combined with chemotherapy were numerically higher, and across tumor stage and PD-L1 expression subgroups.

Ivonescimab + chemotherapy cohort: pCR rate was 43.6%, MPR rate was 71.8%. 69.2% of patients are with residual viable tumor (RVT) ＜ 5%.
As of Aug, 2024, 55 patients in this cohort completed surgery, pCR and MPR rates were improved to 52.7% and 72.7%, respectively. For squamous NSCLC, pCR and MPR rates were 63.6% and 84.1%, respectively.
Ivonescimab monotherapy cohort: pCR rate was 30.0%, MPR rate was 60.0%.
Event-Free Survival (EFS) is not mature yet. Related studies have point to a strong correlation between pCR and EFS.

The safety profile was manageable. There were no TRAEs that led to cancelled or delayed surgery or wound healing complications.

About Ivonescimab

Ivonescimab is a novel global first-in-class PD-1/VEGF bi-specific immunotherapy drug internally developed by Akeso. Ivonescimab has been approved in China for treating EGFR mutated locally advanced or metastatic non-squamous NSCLC patients who have progressed after EGFR TKI treatment. It is the world’s first approved bispecific antibody with a "cancer immunotherapy + anti-angiogenesis" synergistic mechanism.

Akeso out-licensed Summit Therapeutics exclusive rights to ivonescimab for the development and commercialization in certain territories including United States, Canada, Europe, Japan, Latin America, Africa and the Middle East. Ivonescimab is known as AK112 within Akeso and SMT112 in the territories licensed to Summit.

Currently, a Phase III study of ivonescimab monotherapy versus pembrolizumab monotherapy as first-line treatment for PD-L1+ NSCLC has met its primary endpoint of progression-free survival (PFS) in an interim analysis, achieving a decisive positive outcome. Based on this study, a supplemental New Drug Application (sNDA) for ivonescimab monotherapy as first-line treatment for PD-L1+ NSCLC has been submitted and granted priority review. Additionally, a Phase III clinical study of ivonescimab combined with chemotherapy versus tislelizumab combined with chemotherapy as first-line treatment for squamous NSCLC is ongoing. The HARMONi study, an international multicenter Phase III clinical study led by Akeso’s partner Summit, is investigating ivonescimab combined with chemotherapy for EGFR-mutated, locally advanced or metastatic nsq-NSCLC that has progressed after third-generation EGFR-TKI therapy. Another international multicenter Phase III study is comparing ivonescimab combined with chemotherapy to pembrolizumab combined with chemotherapy as first-line treatment for squamous NSCLC.

Furthermore, 3 new Phase III clinical studies are either initiated or about to start, including ivonescimab combined with AK117 (CD47) as first-line treatment for PD-L1 positive squamous cell carcinoma of the head and neck (vs. pembrolizumab), ivonescimab combined regimen as first-line treatment for cholangiocarcinoma (vs. durvalumab combined regimen), and ivonescimab combined regimen as first-line treatment for pancreatic cancer. Overall, ivonescimab is engaged in over 25 clinical trials across 17 indications, including lung cancer, pancreatic cancer, breast cancer, hepatocellular carcinoma, and colorectal cancer, through both monotherapy and combination therapy approaches.