HONG KONG,Dec. 4,2024 -- Akeso,Inc. (9926.HK) ("Akeso" or the "Company") announced the results from a prospective,open-label,single-arm,multi-center phase Ib/II clinical study (AK104-IIT-018) of cadonilimab (PD-1/CTLA-4 bispecific antibody) in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who had progressed after prior PD-(L)1 inhibitor treatment,were presented at the 2024 Asian Conference on Lung Cancer (ACLC).

Professor Han Baohui from Shanghai Chest Hospital presented the initial positive results of the cadonilimab combination therapy for immune-resistant NSCLC at the conference. The treatment demonstrated a 6-month progression-free survival (PFS) rate of 56.9%,a median PFS of 6.5 months,a disease control rate (DCR) of 94.0%,and a median duration of response (DoR) of 5.0 months. Nearly all patients showed long-lasting tumor control,highlighting cadonilimab as a promising and effective second-line treatment for advanced immune-resistant NSCLC.

The AK104-IIT-018 study is a prospective,multicenter Phase Ib/II clinical trial (NCT05816499) conducted across four centers in China. The study was initated in February 2023,and this report presented the preliminary data analysis. The study enrolled patients with unresectable,incurable locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-small cell lung cancer (NSCLC),who tested negative for driver mutations and had previously received PD-1/L1 inhibitors along with platinum-based doublet chemotherapy (either in combination or sequentially,regardless of sequence),with disease progression. Patients were treated with a combination regimen of cadonilimab (10 mg/kg every 3 weeks),anlotinib,and docetaxel (60 mg/m²). The primary endpoint of the study is the 6-month progression-free survival (PFS) rate.

As of May 31,2024,46 patients had been enrolled in the study. Among these,41.3% had non-squamous NSCLC and 58.7% had squamous NSCLC. Regarding PD-L1 expression,10.9% of patients had levels <1%,28.3% between 1-49%,and 15.2% had PD-L1 expression≥50%. Reflective of the real-world NSCLC patient population,10.9% of patients had brain metastasis,6.5% of the patients had liver metastasis,and 23.9% of the patients had bone metastasis.

Progression-Free Survival (PFS):

As of May 31,the maturity of PFS was 30.4%,with a 6-month PFS rate of 56.9% (compared to 30% for docetaxel monotherapy). The median PFS was 6.5 months (versus 4 months for docetaxel monotherapy).

Tumor Response:

Out of 33 patients,10 achieved partial response (PR),and 21 had stable disease (SD). The overall objective response rate (ORR) was 30.3%,which is significantly higher than the 14% ORR observed in previous studies of docetaxel alone. Among the 10 patients with partial response,the median duration of response (DoR) was 5.0 months.

Disease Control Rate (DCR):

The DCR reached 94.0%,with nearly all patients experiencing effective tumor control.

Safety:

The combination of cadonilimab,and docetaxel for treating advanced,driver gene-negative,immune-resistant NSCLC was well-tolerated. The adverse events were manageable and controllable,and the safety profile was favorable.

For patients with advanced,driver gene-negative NSCLC who progress after first-line immunotherapy combined with chemotherapy,treatment options are limited. The standard treatment recommended by the NCCN guidelines is single-agent chemotherapy,but its efficacy is limited,with an objective response rate (ORR) of 14%–17%,a 6-month progression-free survival (PFS) rate of approximately 30%,PFS of 4.0–5.4 months,and overall survival (OS) of 10.5–12 months. The cadonilimab regimen holds potential as a new treatment option for immune-resistant NSCLC. Cadonilimab is a bispecific antibody that targets both PD-1 and CTLA-4,and is independently developed by Akeso. It is a humanized immunoglobulin G1 (IgG1) bispecific antibody (BsAb). Cadonilimab promotes "immune normalization" in the tumor microenvironment through multiple mechanisms. Its unique tetravalent symmetric structure design and Fc modifications enable enhanced accumulation in tumor tissues. As a result of this study,cadonilimab demonstrated the potential to improve the efficacy of tumor immunotherapy while reducing adverse reactions.

Akeso has conducted several clinical trials to evaluate cadonilimab in the treatment of immune-resistant or poorly responsive tumors. These include the registrational phase III trial (AK109-301) of cadonilimab combined with its VEGFR-2 monoclonal antibody for advanced gastric cancer progressing after PD-1/L1 inhibitors plus chemotherapy,and the phase III trial (AK104-307) comparing cadonilimab plus chemotherapy to tislelizumab plus chemotherapy as first-line treatment for PD-L1-negative NSCLC.

About Akeso

Akeso (HKEX: 9926.HK) is a leading biopharmaceutical company committed to the research,development,manufacturing and commercialization of the world's first or best-in-class innovative biological medicines. Founded in 2012,the company has created a unique integrated R&D innovation system with the comprehensive end-to-end drug development platform (ACE Platform) and bi-specific antibody drug development technology (Tetrabody) as the core,a GMP-compliant manufacturing system and a commercialization system with an advanced operation mode,and has gradually developed into a globally competitive biopharmaceutical company focused on innovative solutions. With fully integrated multi-functional platform,Akeso is internally working on a robust pipeline of over 50 innovative assets in the fields of cancer,autoimmune disease,inflammation,metabolic disease and other major diseases. Among them,22 candidates have entered clinical trials (including 11 bispecific/multispecific antibodies and bispecific antibody-drug conjugates). Additionally,5 new drugs are commercially available,and 5 new drugs across 7 indications are currently under regulatory review for approval. Through efficient and breakthrough R&D innovation,Akeso always integrates superior global resources,develops the first-in-class and best-in-class new drugs,provides affordable therapeutic antibodies for patients worldwide,and continuously creates more commercial and social values to become a global leading biopharmaceutical enterprise.

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