Akeso's Cadonilimab Combo for PD-(L)1 Resistant NSCLC at 2024 Asian Lung Cancer Conference

HONG KONG, Dec. 4, 2024 – Akeso, Inc. (9926.HK), a prominent biopharmaceutical company, has revealed results from their phase Ib/II clinical study (AK104-IIT-018) of cadonilimab, a PD-1/CTLA-4 bispecific antibody, aimed at patients with advanced or metastatic non-small cell lung cancer (NSCLC) who had not responded to prior PD-(L)1 inhibitor treatments. These findings were presented at the 2024 Asian Conference on Lung Cancer (ACLC).

Professor Han Baohui of Shanghai Chest Hospital shared the initial promising outcomes of combining cadonilimab with other therapies for immune-resistant NSCLC. Notably, the treatment showed 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. These results underscored cadonilimab's potential as an effective second-line treatment for advanced immune-resistant NSCLC, with nearly all patients demonstrating prolonged tumor control.

The AK104-IIT-018 study, which began in February 2023, is a prospective, open-label, single-arm, multicenter Phase Ib/II clinical trial conducted in four centers across China. This report covers the preliminary data analysis. The study involved patients with unresectable, incurable locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-small cell lung cancer who had tested negative for driver mutations and had previously received PD-1/L1 inhibitors along with platinum-based doublet chemotherapy. The primary endpoint is the 6-month PFS rate.

As of May 31, 2024, the study had enrolled 46 patients. Among these, 41.3% had non-squamous NSCLC, while 58.7% had squamous NSCLC. Regarding PD-L1 expression levels, 10.9% had levels below 1%, 28.3% had levels between 1-49%, and 15.2% had levels of 50% or higher. Reflecting real-world NSCLC patient demographics, 10.9% had brain metastasis, 6.5% had liver metastasis, and 23.9% had bone metastasis.

The maturity of PFS was at 30.4%, with a 6-month PFS rate of 56.9%, which is significantly higher compared to the 30% rate for docetaxel monotherapy. The median PFS was 6.5 months, compared to 4 months for docetaxel alone. Tumor response data revealed that out of 33 evaluable patients, 10 achieved partial response (PR) and 21 had stable disease (SD), resulting in an overall objective response rate (ORR) of 30.3%. This was notably higher than the 14% ORR seen in prior studies of docetaxel monotherapy. Among those with partial response, the median DoR was 5.0 months. The DCR reached 94.0%, indicating effective tumor control in most patients.

The combination treatment of cadonilimab, anlotinib, and docetaxel showed a favorable safety profile, with manageable and controllable adverse events.

Patients with advanced, driver gene-negative NSCLC who do not respond to first-line immunotherapy combined with chemotherapy have limited options. The standard treatment recommended by the NCCN guidelines is single-agent chemotherapy, but its efficacy is restricted, with an ORR of 14%–17%, a 6-month PFS rate of around 30%, a PFS of 4.0–5.4 months, and an overall survival (OS) of 10.5–12 months. The cadonilimab regimen presents a new potential treatment for immune-resistant NSCLC. Cadonilimab, developed by Akeso, is a humanized immunoglobulin G1 (IgG1) bispecific antibody targeting PD-1 and CTLA-4. It enhances "immune normalization" in the tumor microenvironment through multiple mechanisms, with a unique tetravalent symmetric structure and Fc modifications that promote tumor tissue accumulation. This study highlights cadonilimab’s potential to improve tumor immunotherapy efficacy while reducing adverse reactions.

Akeso has undertaken multiple clinical trials to assess cadonilimab’s efficacy in treating immune-resistant or poorly responsive tumors. These include a registrational phase III trial (AK109-301) for advanced gastric cancer and a phase III trial (AK104-307) for first-line treatment of PD-L1-negative NSCLC.

Akeso, founded in 2012, is dedicated to the research, development, manufacturing, and commercialization of innovative biological medicines. The company boasts a robust R&D system and over 50 innovative assets in its pipeline, with 22 candidates in clinical trials. Akeso aims to develop first-in-class and best-in-class new drugs, providing affordable therapeutic antibodies globally, and continues to create substantial commercial and social value.