HONG KONG, Oct. 12, 2023 /PRNewswire/ -- Akeso, Inc. (9926.HK) ("Akeso") announced that the results of the multicenter, open-label Phase Ib/II clinical trial (COMPASSION-03/AK104-201) for cadonilimab (PD-1/CTLA-4 bispecific antibody), the globally first bispecific IO drug used to treat advanced solid tumors, have been published in the October 2 issue of The Lancet Oncology. This multicenter clinical trial marks the first utilization of PD-1/CTLA-4 dual immune checkpoint inhibitors in the treatment of advanced solid tumors.

Cadonilimab is the first-in-class PD-1/CTLA-4 bispecific antibody developed in China. Cadonilimab possesses high binding avidity especially to high density of PD-1 and CTLA-4 due to its tetravalent design and could simultaneously bind different cells expressing PD-1 and CTLA-4, respectively, thereby reducing the activation of the relevant immunosuppressive pathways by tumor cells and enhance the T-cell-mediated immune response. Previous clinical trials confirmed the synergistic anti-tumor effect of cadonilimab's novel combination therapy of PD-1/CTLA-4. This, along with its favorable safety profile, offers promising prospects for ushering in the era of tumor immunotherapy 2.0.

The COMPASSION-03/AK104-201 trial assessed the efficacy and safety of cadonilimab, both as a monotherapy for advanced solid tumors and in combination with chemotherapy for unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. It represents a significant milestone in the global advancement of oncology treatment, particularly in patients diagnosed with advanced cervical cancer. The study produced important efficacy evidence for the clinical development and approval of cadonilimab, supporting further investigation of cadonilimab across multiple indications.

The results of combined therapy in patients with G/GEJ adenocarcinoma will be reported separately at a later date since the data from the combination treatment cohort are not yet mature. It is worth noting that the 2-year follow-up update data from the previous phase Ib/II clinical trial of cadonilimab in combination with chemotherapy for the first-line treatment of G/GEJ adenocarcinoma was presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. The distinct and superior efficacy of cadonilimab in the PD-L1 low-expression or expression-negative population further suggests that cadonilimab holds promise for successive therapies in the first-line treatment of clinically advanced gastric cancer.

This publication in the Lancet Oncology presents data from a study involving 240 patients who received cadonilimab monotherapy. Among them, 83 patients with advanced solid tumors, including gastric cancer, cervical cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma, colorectal cancer, non-small cell lung cancer, and renal cancer, were enrolled in phase Ib. A total of 157 patients were enrolled in phase II, which consisted of three cohorts. Cohort 1 consisted of 111 patients with recurrent or metastatic cervical cancer (CC) who had previously failed platinum-based chemotherapy; cohort 2 consisted of 24 patients with advanced hepatocellular carcinoma (HCC) who had received no more than one previous systemic therapy; and cohort 3 consisted of 22 patients with advanced esophageal squamous cell carcinoma (ESCC) who had received no more than one previous systemic therapy.

No dose-limiting toxicities occurred during the dose-escalation phase of Phase Ib, and the overall safety profile of cadonilimab was favorable. The incidence of grade 3-4 treatment-related adverse events (TRAEs) was 27.9%, and the most frequently reported grade ≥3 TRAEs consisted of anemia, decreased appetite, decreased neutrophil count, and infusion-related reactions.

The monotherapy of cadonilimab in phase II demonstrated promising antitumor activity, resulting in a notable long-term survival advantage.

• After a median follow-up duration of 14.6 months, as assessed by the Independent Radiology Review Committee, the objective response rate (ORR) for cadonilimab monotherapy in patients with advanced CC who had previously failed platinum-based chemotherapy was 32.3%, 14 (14.1%) patients had a complete response (CR) and 18 patients (18.2%) had a partial response (PR). The median overall survival (OS) was not reached, and the 18-month OS reached 51.2%. These cohort data were presented at the 2022 American Society of Gynecologic Oncology (SGO) meeting, sparking extensive discussions within the global oncology scholarly community.
• After a median follow-up duration of 17.9 months, the median OS was 9.4 months for cadonilimab monotherapy in patients with advanced ESCC who had received no more than one previous systemic therapy , and six patients were censored after 14 months.
• After a median follow-up duration of 19.6 months, the median OS had not reached for cadonilimab monotherapy in patients with advanced HCC who had received no more than one previous systemic therapy, and the 18-month OS was 56.7%.

In June 2022, cadonilimab received conditional approval from the China National Medical Products Administration (NMPA) for commercialization, for the treatment of recurrent or metastatic cervical cancer. This milestone establishes cadonilimab as the first approved bispecific immunotherapy drug and marks its distinction as the first domestically-produced bispecific antibody to receive marketing approval in China. These achievements represent significant progress in bridging the global gap in bispecific antibody drugs for cancer immunotherapy and immunotherapy drugs for advanced cervical cancer in China.

In addition, the phase III clinical trial (AK104-302, NCT05008783) investigating cadonilimab in combination with chemotherapy as a first-line treatment for advanced G/GEJ adenocarcinoma, led by Prof. Jafu Ji and Prof. Lin Shen from Peking University Cancer Hospital, has completed enrollment and entered the follow-up phase. Additionally, the randomized, double-blind, placebo-controlled phase III clinical trial (AK104-303, NCT04982237) evaluating the efficacy of cadonilimab combined with platinum-based chemotherapy +/- bevacizumab for the first-line treatment of recurrent/metastatic cervical cancer has also completed enrollment and entered the follow-up phase.

Read the full article in the latest issue of The Lancet Oncology:https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00411-4/fulltext

The COMPASSION-03/AK104-201 study was jointly conducted by Professors Jiafu Ji and Lin Shen from Peking University Cancer Hospital, as well as Professor Xiaohua Wu from Fudan University Shanghai Cancer Center.