Akeso, Inc. (9926.HK) ("Akeso" or the "Company") is pleased to announce that the first patient has been successfully enrolled in the registration Phase III clinical trial (AK112-312/HARMONi-GI6) of ivonescimab in first-line treatment for advanced metastatic colorectal cancer (mCRC).

This randomized, controlled, multi-center Phase III clinical trial for first-line treatment of mCRC is one of the company's key initiatives to address the significant unmet clinical need worldwide with ivonescimab.

Colorectal cancer remains the third most common cancer globally and the second leading cause of cancer-related deaths. In 2022, over 1.9 million new cases were reported, with approximately 904,000 deaths. Of these, about 95% of mCRC cases are classified as microsatellite stable (MSS) or proficient mismatch repair (pMMR), which traditionally show poor responses to immunotherapy and the tumors are often referred to as an "immune desert."

For first-line treatment of MSS/pMMR-type mCRC, which represents up to 95% of cases, several PD-1/L1 inhibitors have been explored in multiple international studies. However, the efficacy has been limited, and as of now, no first-line immunotherapy has been approved globally for patients with pMMR/MSS-type mCRC.

Chemotherapy combined with targeted therapies (such as bevacizumab, cetuximab, etc.) remains the standard first-line treatment for mCRC, though its overall efficacy is limited, with a five-year survival rate for advanced patients of less than 20%. Bevacizumab is the most well-established and clinically impactful treatment in the mCRC space. It is also one of the core indications of bevacizumab.

At the 2024 European Society for Medical Oncology (ESMO) Congress, Professor Yanhong Deng from the Sixth Affiliated Hospital of Sun Yat-sen University, presented promising Phase II efficacy data of ivonescimab in combination with chemotherapy for first-line treatment of MSS/pMMR-type mCRC.

The combination of ivonescimab with FOLFOXIRI demonstrated compelling anti-tumor activity in this hard to treat patient population, with an overall response rate (ORR) of 81.8% and a disease control rate (DCR) of 100%. After a median follow-up of 9 months, the median progression-free survival (mPFS) was not reached, with a 9-month PFS rate of 81.4%. Regardless of KRAS/BRAF mutation status, patients can benefit from ivonescimab combination therapy.

The results published at the 2024 ESMO suggest that ivonescimab may offer a significant improvement over existing treatment options for MSS/pMMR mCRC patients. The Phase III trial AK112-312/HARMONi-GI6 can potentially further validate the clinical benefits of ivonescimab in this setting, offering a novel first-line immunotherapy treatment option for patients with advanced mCRC.