Phase Ib/II Results of Akeso's PD-1/CTLA-4 Bispecific Antibody for First-Line Treatment of Advanced Hepatocellular Carcinoma Published at 2023 ESMO

HONG KONG, Oct. 24, 2023 /PRNewswire/ — Akeso announced poster presentation at the 2023 European Society for Medical Oncology (ESMO) Congress from its cadonilimab ( PD-1/CTLA-4 bispecific antibody) combined with lenvatinib for first-line treatment of Advanced Hepatocellular Carcinoma (HCC). The principal investigators of the study are Prof. Bai Li and Prof. Jiao Shunchang of the Chinese PLA General Hospital.

The results indicated that the novel combination therapy of PD-1/CTLA-4 bispecific antibody plus lenvatinib demonstrated promising efficacy and manageable toxicity that could provide an option of treatment in first-line treatment of advanced HCC. At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Akeso presented the preliminary therapeutic effect of cadonilimab combined with lenvatinib for first-line therapy of advanced HCC, showing promising anti-tumor activity and improved tolerability. The 2 years median follow-up results presented at the 2023 ESMO meeting further emphasized the efficacy of cadonilimab in improving overall survival (OS) among advanced patients.

Data Highlights:

Results demonstrated the outstanding efficacy of cadonilimab when combined with lenvatinib as a first-line treatment for HCC. The preliminary efficacy data outperformed those of approved therapies. As of July 28, 2023, the median follow-up period was 27.4 months.

  • When cadonilimab was dosed at 6 mg/kg Q2W, the objective response rate (ORR) was 35.5%, the median duration of response (mDoR) was 13.6 months, the median progression free survival (mPFS) was 8.61 months, and mOS was 27.1 months.
  • When the dose of cadonilimab was 15 mg/kg Q3W, the ORR was 35.7%, the mDoR was 13.7 months, the mPFS was 9.82 months, and the mOS was not yet reached.
  • The mPFS for first-line HCC treatment with the combination of cadonilimab and lenvatinib was higher compared to approved therapies. The study indicated that the improvement in PFS was more significant with the higher dose of cadonilimab (8.6 months at 6 mg/kg every 2 weeks vs. 9.8 months at 15 mg/kg every 3 weeks).
  • The adverse effects of the combination of cadonilimab and lenvatinib at all dosage levels were readily manageable without any new safety signals or cadonilimab-associated fatalities.

Akeso is currently conducting a randomized, double-blind, controlled Phase III clinical trial (AK104-306, NCT05489289) to evaluate the efficacy and safety of cadonilimab as adjuvant therapy for high-risk hepatocellular carcinoma after curative resection. The potential efficacy of cadonilimab for both operable and advanced HCC holds great promise for improving long-term survival rates for the entire HCC population.

About Cadonilimab(PD-1/CTLA-4 bispecific antibody)

Cadonilimab is a first-in-class bispecific antibody that targets both PD-1 and CTLA-4 developed by Akeso. It is a symmetric tetravalent bispecific antibody with a crystallizable fragment (Fc)-null design. In addition to demonstrating biological activity similar to that of the combination of CTLA-4 and PD-1 antibodies, cadonilimab possesses higher binding avidity in a high-density PD-1 and CTLA-4 setting than in a low-density PD-1 setting, while a mono-specific anti-PD-1 antibody does not demonstrate this differential activity. With no binding to Fc receptors, cadonilimab shows minimal antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and interleukin-6 (IL-6)/IL-8 release. These features all likely contribute to significantly lower toxicities of cadonilimab observed in the clinic. Higher binding avidity of cadonilimab in a tumor-like setting and Fc-null design may lead to better drug retention in tumors and contribute to better safety while achieving anti-tumor efficacy.

Cadonilimab has been approved by the China National Medical Products Administration for recurrent or metastatic cervical cancer. Cadonilimab has been included and recommended in multiple clinical guidelines such as CSCO. In its first 12 months on the market, cadonilimab generated impressive sales revenue of 1.15 billion RMB. Cadonilimab has been engaged in more than 60 ongoing clinical trials including investigator-initiated studies. Patient enrollment has been completed for the phase 3 study of cadonilimab for first-line treatment of advanced cervical cancer as well as a phase 3 study of cadonilimab in combination with chemotherapy as first-line therapy in gastric cancer. A phase 3 study of cadonilimab as an adjuvant treatment for hepatocellular carcinoma is ongoing. Furthermore, a Phase 3 study comparing cadonilimab with chemotherapy to tislelizumab Injection with chemotherapy is underway for the first-line treatment of PD-L1 expression-negative non-small cell lung cancer.

About Akeso, Inc.

Akeso (HKEX: 09926) is a commercial-stage biopharmaceutical company committed to discovering, developing, manufacturing, and commercializing innovative medicines that address significant medical needs globally. Since our inception , we have established a distinctive and 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 fundamental components, a GMP-compliant manufacturing system and a commercialization system with an advanced operation mode.

Akeso is actively developing a diverse pipeline of over 30 innovative assets in areas such as cancer, autoimmune disease, inflammation, metabolic disease, and other therapeutic fields. Among these, 19 assets have entered the clinical stage, with 3 innovative drugs already approved, NDAs for 4 drugs and 6 indications accepted, and 13 ongoing Phase III studies. Utilizing its proprietary Tetrabody technology, Akeso has successfully developed the first-in-class PD-1/CTLA-4 bispecific antibody drug to the market. Additionally, the company has five other innovative bispecific antibody drugs in the clinical stage, including ivonescimab (PD-1/VEGF), PD-1/LAG-3, TIGIT/TGF-Beta, PD-1/CD73, and claudin18.2/CD47 bispecific antibodies.

In June 2022, cadonilimab was approved by the NMPA and became the first commercialized bispecific IO drug globally. Another Akeso internally discovered and developed oncology product, penpulimab (a PD-1 antibody), was granted marketing approval in China in August 2021. In December 2022, Akeso entered into a collaboration and license agreement for up to US$5 billion with Summit Therapeutics to accelerate global development and commercialization of ivonescimab. In August, the NDA submission of ivonescimab was accepted by China’s NMPA and granted Priority Review. Akeso is listed on the Main Board of the Stock Exchange of Hong Kong Limited.


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Source: Phase Ib/II Results of Akeso's PD-1/CTLA-4 Bispecific Antibody for First-Line Treatment of Advanced Hepatocellular Carcinoma Published at 2023 ESMO