96P - Cadonilimab combined with taxane and cisplatin as the first-line treatment of advanced esophageal squamous cell carcinoma (ESCC): an open-label, multicenter phase ? trial (AK104-IIT-014)

Background

Chemotherapy combined with anti-PD-1 monoclonal antibody has already become the first-line treatment in advanced ESCC, while the benefits in objective responses and survival were limited. Cadonilimab (AK104), a bispecific antibody simultaneously targeting PD-1 and CTLA-4, was designed to boost anti-tumour activity with an improved safety profile. Here, we first evaluated the safety and efficacy of AK104 combination therapy as the first-line treatment in advanced ESCC.

Methods

Eligible pts with previously untreated unresectable locally advanced or metastatic ESCC received AK104 (10mg/kg, iv, d1, q3w) combined with paclitaxel or nab-paclitaxel (175 mg/m², iv, d1, q3w) and cisplatin (65 to 75 mg/m², iv, d1, q3w) for up to 6 cycles, then continued AK104 (10mg/kg, iv, d1, q3w) treatment as maintenance until progressive disease or unacceptable toxicity, with a maximum of 24 months. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety.

Results

As of data cut-off (September 21, 2023), 22 pts were enrolled with a median age of 61 years (range 44-75), 50.0% had PD-L1 CPS<10. In the efficacy-evaluable population (n=15), 13 pts reached partial response and 2 pts had stable disease. The ORR was 86.7% (95%CI: 58.4%-97.7%) and the DCR was 100.0% (95%CI: 74.7%-100%). Both median PFS and OS were not reached. Among evaluable pts with PD-L1 CPS≥10 and PD-L1 CPS<10, the ORR were 83.3% (5/6) and 88.9% (8/9), respectively. Seven (31.8%) pts experienced grade 3-4 TRAEs, which mainly included neutropenia (22.7%), leukopenia (9.1%) and hyponatremia (9.1%). Immune-related AEs were observed in 3pts (13.6%). 3 pts (13.6%) suffered from serious AEs, and no grade 5 TRAE was observed. AEs led to discontinuation of AK104 in 2 (9.1%) of enrolled pts.

Conclusions

Bispecific antibody AK104 combined with taxane and cisplatin showed better ORR and manageable safety as first-line treatment in advanced ESCC, regardless of PD-L1 expression. Survival outcomes will be reported in the future and single AK104 cohort in pts with PD-L1 CPS≥5 ESCC is being explored.

Clinical trial identification

NCT05522894.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.