1446P - Efficacy and safety of cadonilimab combined albumin-paclitaxel, cisplatin and fluorouracil (APF) in neoadjuvant therapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC): Results from the CAPITAL trial

Background

Neoadjuvant therapy with Docetaxel, Cisplatin, and 5-FU (DCF) is established as the standard treatment for LA-ESCC as per JCOG1109. Immunotherapy for LA-ESCC has been rapidly explored. Cadonilimab (AK104), a first-in-class bispecific antibody targeting PD-1 and CTLA-4, has shown promising efficacy and tolerability. This study aimed to assess the efficacy and safety of AK104 combined with modified APF in neoadjuvant therapy for LA-ESCC.

Methods

In this prospective, single-arm, phase II clinical trial (NCT05947201), we enrolled patients (pts) aged 18-75 with histologically diagnosed with ESCC and primary lesion located within the thoracic esophagus (cT1N1-3M0/cT2-3N0-3M0, AJCC 8th). Pts received 2–3 cycles of neoadjuvant therapy with AK104 combined with modified APF (AK104 [day 1]: 10 mg/kg, nab-PTX [day 1/8]: 100 mg/m2, CDDP [day 1-3]: 20 mg/ m2, 5-FU [continuous infusion on days 1-5]: 600 mg/m2, every 3 weeks). Surgery was performed 4-6 weeks after the last cycle. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included major pathologic response (MPR), tumor regression grade, R0 resection rate, non-surgery-delay rate, event-free survival, disease-free survival, overall survival, and toxicities.

Results

Twenty-one pts were enrolled and received neoadjuvant therapy between May, 2023 and May, 2024, 11 of whom proceeded to surgical resection. The rate of pCR and MPR were 36% (4/11) and 54% (6/11), respectively. R0 resection rate was 100%, with all surgical procedures conducted as scheduled. No treatment-related death has occurred so far. Treatment-related adverse events (TRAEs) were observed in 80.9% (17/21) of pts, with 28.5% (6/21) experiencing grade ≥3 events. Immune related adverse events included skin rash (4 pts grade 1/2; 1 pt grade 3/4) and hypothyroidism (3 pts grade 1/2).

Conclusions

AK104 combined with modified APF is a promising neoadjuvant treatment for resectable LA-ESCC, demonstrating antitumor activity and an acceptable safety profile. Meanwhile, long-term survival outcomes are pending further follow-up.

Clinical trial identification

NCT05947201.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Akeso Pharmaceuticals, Inc. provided the study drug AK104.

Disclosure

All authors have declared no conflicts of interest.