HONG KONG, China I January 30, 2022 I Akeso, Inc. (9926.HK) announces that the first patient was dosed in a Phase III registrational clinical trial of the Company’s novel immuno-oncology drug, Ivonescimab (PD-1/VEGF bi-specific antibody, AK112), combined with chemotherapy versus placebo combined with chemotherapy for the treatment of locally advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) with EGFR mutation failed after EGFR-TKI treatment.

This clinical trial is the world’s first bi-specific antibody for the Phase III clinical trial of EGFR-TKI resistant NSCLC, and is also an important development of Ivonescimab in the field of lung cancer.

This clinical trial is a randomized, double-blind, multi-center Phase III clinical study with approximately 320 Chinese subjects planned to be enrolled. The purpose of the study is to evaluate the efficacy and safety of Ivonescimab combined with pemetrexed + carboplatin and placebo combined with pemetrexed + carboplatin in the treatment of patients with advanced nsq-NSCLC resistant to EGFR-TKI. The primary endpoint of the study is progression-free survival (PFS) assessed by IRRC.

Lung cancer is a common malignant tumor with high incidence and high mortality in the world, with the number of new lung cancer cases in the world exceeding 2,200,000 in 2020, and the number of new cases in China exceeding 810,000. By type, NSCLC accounts for about 85% of lung cancer, of which about 75% is non-squamous cell NSCLC, and about 70% of NSCLC patients are diagnosed at an advanced stage (Phase IIIB/IV).

For patients with EGFR mutation or ALK fusion mutation-positive NSCLC, although targeted therapy is a first-line standard therapy, issue of drug resistance has become increasingly prominent, and if resistant to targeted therapy, platinum-based chemotherapy remains the most important treatment method, and the existing treatment options cannot effectively meet clinical needs.

”Immunotherapy + anti-angiogenesis” has proven its combined advantages in several worldrenowned studies. As anti-angiogenic therapy can normalize tumor blood vessels and make the tumor microenvironment more suitable for immunotherapy, Immunosuppressants combined with anti-angiogenic drugs has a synergistic anti-tumor effect. This combination is widely appreciated. Lung cancer treatment is the main exploration direction of the above combination therapy; The ”immune + anti-angiogenesis” combination therapy under development in the world for first-line and later-line treatment of NSCLC has shown promising anti-tumor activity and clinical application prospects.

Ivonescimab also has the effect of stimulating antitumor immune responses and inhibiting tumor angiogenesis. Because of the immunosuppressive effect of the overexpressed VEGF in the tumor microenvironment, if a bi-specific antibody can be used to block both PD-1 and VEGF, theoretically the synergistic anti-tumor effect of anti-PD-1 antibody and anti-VEGF antibody can be realized. As a result, Ivonescimab with chemotherapy for the treatment of EGFR-TKI resistant NSCLC is expected to achieve better clinical efficacy and safety than other therapies.

In a number of early clinical studies in Australia and China, Ivonescimab has demonstrated good safety and tolerability in the treatment of various types of lung cancer, including NSCLC and small cell lung cancer (SCLC), with excellent anti-tumor effects. In addition to this study, Ivonescimab’s Phase III clinical trial for the first-line treatment of PD-L1positive NSCLC and Ivonescimab’s Phase III clinical trial for the first-line treatment of extensive SCLC will commence soon. The Phase Ib/II clinical study of Cadonilimab (PD-1/ CTLA-4 bi-specific antibody, AK104) plus Ivonescimab and/or in combination with chemotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) has also been carried out successively.