Abstract 1207P
Background
Neoadjuvant concurrent chemoradiotherapy remains the standard treatment for locally advanced ESCC. Recent studies also revealed survival benefit from neoadjuvant chemotherapy alone while with limited pathological complete response (pCR) rate. This phase IB/II study aimed to evaluate the safety and efficacy of neoadjuvant Socazolimab, a novel PD-L1 inhibitor, combined with nab-paclitaxel/cisplatin for locally advanced ESCC.
Methods
Patients (pts) with ESCC (cT2N+M0 or cT3-4aN+/-M0) were enrolled. Following the safety evaluation in the phase IB stage, pts were randomly assigned 1:1 in the phase II stage, receiving either Socazolimab (5mg/kg IV, day 1, S arm) or placebo (P arm) with nab-paclitaxel (125mg/m2 IV, day 1/8) and cisplatin (75mg/m2 IV, day 1) repeated every 21 days for 4 cycles before surgery. Pts in S arm with pathological residues after surgery continued Socazolimab for another 12 cycles. The primary endpoint was major pathological response (MPR), and secondary endpoints were pCR, R0 resection rate, event free survival (EFS), overall survival (OS) and safety.
Results
In the phase IB stage, no dose limiting toxicities were observed in the first 6 pts. Sixty-four pts were subsequently assigned to S arm (n=32) and P arm (n=32) in the phase II stage. At time of Jan 5, 2022, 29 (90.6%) pts in both arms received surgery, 29 (100%) and 28 (98.6%) pts underwent R0 resection in S arm and P arm, respectively. The MPR rates were 68.97% and 62.07% (p=0.509) and the pCR rates were 41.4% and 27.6% (p=0.311) respectively. A significantly higher incidence of ypT0 was observed in S arm (37.93% vs 3.45%; P=0.001). Data of EFS and OS is not mature. The incidences of grade 3 or higher treatment-related adverse events (AEs) were 65.5% and 62.5% respectively. The most common AEs were neutropenia (59.4% vs 56.3%), leukopenia (43.8% vs 25.0%), and hypokalemia (18.8% vs 0). Major surgical complications occurred in 2 pts in each arm.
Conclusions
Neoadjuvant Socazolimab with chemotherapy demonstrated outstanding MPR and pCR rates in locally advanced ESCC without increasing perioperative complications. This strategy warrants further investigations in phase III trials.
Clinical trial identification
NCT04460066.
Editorial acknowledgement
Legal entity responsible for the study
Chinese Academy of Medical Sciences.
Funding
Lee's Pharmaceutical Limited.
Disclosure
All authors have declared no conflicts of interest.