131P - The efficacy and safety of cadonilimab with or without trastuzumab in combination with SOX as first-line (1L) treatment for advanced gastric (G) or gastroesophageal Junction adenocarcinoma (GEJA)

Background

PD-1 inhibitors plus chemotherapy was approved as standard 1L treatment for advanced HER2-negative G/GEJA, but its outcomes remain poor in patients (pts) with low PD-L1 expression. For advanced HER2-positive G/GEJA, integrating immunotherapy with trastuzumab and chemotherapy has shown a significant improvement in progression-free survival (PFS) and overall survival (OS). Cadonilimab, a PD-1/CTLA-4 bispecific antibody, has demonstrated its efficacy and safety in previously untreated advanced G/GEJA pts, even those with PD-L1 CPS<5 in a phase III study. Currently, cadonilimab plus XELOX as 1L treatment for advanced G/GEJA was approved by NMPA. This phase II trial was to assess the efficacy and safety of cadonilimab with or without trastuzumab in combination with SOX in advanced G/GEJA.

Methods

Untreated G/GEJA pts received cadonilimab+SOX (HER2-negative pts) or cadonilimab+trastuzumab+ SOX (HER2-positive pts) for up to 6 cycles, followed by maintenance with S-1+cadonilimab with (HER2-positive pts) or without trastuzumab (HER2-negative pts) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR), and secondary endpoints were disease control rate (DCR), PFS, OS, and safety.

Results

As of September 24, 2024, 19 pts were enrolled, of which 13 (68.4%) were HER2 negative and 6 (31.6%) were HER2 positive. The median age was 62.0 (range: 21-74) and 8 (42.1%) were PD-L1 CPS＜5 and HER2 negative. One pt had no post-baseline tumor assessment in HER2-negative pts. Among HER2-positive pts, 6 reached PR, the ORR and DCR were both 100.0%. Of the HER2-negative pts, 6 were PR and 6 exhibited SD, the ORR was 50.0% (6/12) and DCR was 100.0% (12/12). Among HER2-negative pts with PD-L1 CPS＜1, the ORR was 57.1% (4/7) and DCR was 100.0% (7/7). Median PFS and OS were not mature. 3 pts (15.0%) developed grade 3 treatment-related adverse events (TRAEs). There were no grade 4/5 TRAEs.

Conclusions

Cadonilimab with or without trastuzumab in combination with SOX showed promising efficacy and tolerable safety as 1L treatment in HER2-positive or HER2-negative advanced G/GEJA, particularly a high ORR in HER2-positive group.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.