Promising 2-year updated data from cadonilimab presented at 2023 ASCO highlighting promising efficacy in PD-L1-negative patients

HONG KONG,June 6,2023 -- Akeso,Inc. (9926.HK) ("Akeso") released two-year updated data from a Phase Ib/II clinical study of cadonilimab – a first-in-class PD-1/CTLA-4 bispecific antibody developed by Akeso – in combination with chemotherapy as first-line therapy for advanced gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

Results showed that cadonilimab in combination with chemotherapy in first line treatment of G/GEJ adenocarcinoma,had a high remission rate and promising long-term survival advantage in the all-comers population (regardless of PD-L1 status).

As of October 2022,94 gastric cancer patients were enrolled in the study,of which 50% had a negative expression of PD-L1 (CPS <1) and only 15% of patients had a positive expression (CPS ≥ 5). With a median follow-up of 24 months (94% of subjects experienced at least one post-baseline tumor assessment),the updated data continued to show significant efficacy benefits from previously disclosed data,with even more obvious benefits to patients.

Efficacy：

Remission was efficient in the all-comers population,and overall survival (OS) was significantly high: Median OS was 17.41 months,median progression-free survival (PFS) was 9.2 months,and the 12-month OS rate was 61.4%. The objective response rate (ORR) was 68.2%,and the disease control rate (DCR) was 92%.

Promising efficacy in population with high expression of PD-L1: The median OS of the population with PD-L1 CPS ≥5 was up to 20.24 months,and the median PFS was not reached.

Promising efficacy in population with low expression of PD-L1: The median OS of the PD-L1 CPS <5 population was 17.28 months,along with a median PFS of 7.23 months.

Remarkable efficacy in the PD-L1 expression negative population: In the PD-L1 CPS <1 population,the median OS reached 17.64 months and the median PFS was 8.18 months.

Safety：

No adverse safety signals were observed in comparison to the PD-1 monoclonal antibodies.

Gastric cancer is one of the most prolific malignancies in the world and is the second most common malignancy in China. The benefits of PD-1 monotherapy in combination with chemotherapy as a first-line therapy are still relatively limited compared to chemotherapy for OS and PFS. For example,in real patients with advanced G/GEJ adenocarcinoma in China,approximately 13% and 38%[1] of these are PD-L1 low expressing (CPS 1-4) and (CPS <1),respectively,which comprehensively represent more than half of the total patient population. Thus,there is a huge need for more effective treatments for this patient.

Regardless of PD-L1 status,cadonilimab demonstrated highly effective tumor remission and survival benefits in overall advanced gastric cancer. Furthermore,the differential and superior efficacy of cadonilimab in low-PD-L1-expressing populations compared to currently approved PD-1 monoclonal antibodies further suggest that cadonilimab will be an improved therapy for the first-line treatment of advanced gastric cancer.

Currently,the enrollment of the Phase III study (NCT05008783) for the first-line treatment of advanced G/GEJ adenocarcinoma was completed.

Related Studies

For first-line treatment of advanced gastric cancer,the median OS for the population with CPS≥5 was 75% in the CheckMate649 Chinese subgroup,and the median OS for nivolumab combination chemotherapy was 14.3 months regardless of CPS status; 15.5 months for CPS≥5,10.1 months for CPS<5,and 11.8 months for CPS<1[2-3].

In the ORIENT-16 study,population with CPS ≥5 was 61%. Regardless of CPS status,the median OS was 15.2 months with sintilimab combination chemotherapy. In the population with CPS ≥5,the median OS was 19.2 months.[2,4-5]

References:

[1] Zhang L,Wang Y,Li Z,et al. Clinicopathological features of tumor mutation burden,Epstein-Barr virus infection,microsatellite instability and PD-L1 status in Chinese patients with gastric cancer.Diagn Pathol. 2021;16(1):38. Published 2021 May 1. doi:10.1186/s13000-021-01099-y.

[1] Disclaimer: the study mentioned above is for reference only. It doesn't necessarily represent the latest clinical study ongoing for the same indication,and it is not a head-to-head study derived from AK104clinical trial.

[2] Liu T,Bai Y,Lin X,et al. First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric,gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis.Int J Cancer. 2023;152(4):749-760. doi:10.1002/ijc.34296

[3] J. XU HJ,Y. PAN et al. Sintilimab plus chemotherapy (chemo) versus chemo as first-line treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (ORIENT-16): First results of a randomized,double-blind,phase III study[J]. Annals of Oncology,2021,32(suppl_5): S1283–S1346.

[4]http://cn.innoventbio.com/#/news/471