Cadonilimab (PD-1/CTLA-4 Bispecific Antibody) Met Primary Endpoint of Progression-Free Survival in Phase III Trial for First-Line Treatment of Recurrent/Metastatic Cervical Cancer in All-Comer Patients

HONG KONG, Nov. 27, 2023 /PRNewswire/ -- Akeso (9926. HK) has announced that the AK104-303 Phase III trial, which investigated cadonilimab (Akeso's PD-1/CTLA-4 bispecific antibody) combined with platinum-based chemotherapy +/- bevacizumab, has met one of its primary endpoints of progression-free survival (PFS) for first-line treatment of recurrent/metastatic cervical cancer (R/M CC), with p-value of less than 0.0001.

The AK104-303 trial represents a significant milestone as the first Phase III clinical trial investigating the combination of a PD-1/CTLA-4 bispecific antibody with platinum-based chemotherapy +/- bevacizumab for first-line treatment of recurrent/metastatic R/M CC. The primary endpoints of the study were progression-free survival (PFS) and overall survival (OS) assessed by blinded independent central review (BICR) based on RECIST v1.1 criteria. In the study, approximately 26% of patients had tumors with PD-L1 CPS < 1. Public data indicates that approximately 11% of patients in the KEYNOTE-826 study had PD-L1 CPS < 1.

During a pre-specified interim analysis conducted by an independent data monitoring committee (IDMC) in the intent-to-treat (ITT) population, cadonilimab combined with platinum-based chemotherapy +/- bevacizumab demonstrated a statistically significant and clinically meaningful PFS benefit compared to placebo combined with platinum-based chemotherapy +/- bevacizumab in all-comer patients, irrespective of their PD-L1 status, including both the PD-L1 CPS ≥ 1 and PD-L1 CPS < 1 populations.

A trend in improvement in overall survival (OS), which is the other primary endpoint, was observed for cadonilimab combination versus placebo in combination with platinum-based chemotherapy +/- bevacizumab. Data for OS were not mature at this interim analysis and the trial will continue as planned to assess OS.

The safety profile of cadonilimab remains consistent with previous clinical results with no new safety signals identified.

The successful achievement of the primary endpoint of PFS in the Phase III trial of cadonilimab for first-line cervical cancer is yet another milestone for the drug in first-line therapy, following the earlier achievement of the primary endpoint in first-line gastric cancer and the planned sNDA by Akeso.

In Jun 2022, cadonilimab was approved for second/third line treatment of advanced cervical cancer. With the encouraging outcomes observed in cadonilimab's registration trials across diverse indications, especially in first-line therapies, the potential patient population eligible for cadonilimab is anticipated to expand rapidly. This expansion will effectively harness the clinical value of this novel bispecific immuno-oncology therapy, bringing benefits to a larger number of patients.

"We are delighted to once again witness the remarkable improvement in progression-free survival achieved with cadonilimab in first-line treatment of all-comer patients with advanced cervical cancer," said Dr. Yu Xia, Founder, Chairwoman, President, and CEO of Akeso. "This outcome not only reaffirms the advantages of cadonilimab observed in the Phase II trials of cervical cancer and other trials, particularly in gastric cancer, but also further validates its exceptional clinical value in cancer treatment. We extend our heartfelt appreciation to all the researchers, participants, and patients who contributed to this trial. It is thanks to your efforts and dedication that a broader population of cervical cancer patients in China will have the opportunity to undergo a novel bispecific IO therapy, thereby enhancing treatment effectiveness and improving survival rates."

About Cadonilimab

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 improve safety while achieving anti-tumor efficacy.

The China National Medical Products Administration has approved cadonilimab for recurrent or metastatic cervical cancer. Cadonilimab has been included and recommended in multiple clinical guidelines such as CSCO. Cadonilimab has been engaged in more than 60 ongoing clinical trials including investigator-initiated studies. Phase 3 study of cadonilimab for first-line treatment of gastric cancer has met its endpoint of PFS. 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, 13 Phase III studies ongoing. Utilizing its proprietary Tetrabody technology, Akeso has successfully developed the first-in-class PD-1/CTLA-4 bispecific antibody drug for 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 with priority review. Akeso is listed on the Main Board of the Stock Exchange of Hong Kong Limited.

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SOURCE Akeso, Inc.