A Phase II clinical trial has indicated that the addition of socazolimab, a PD-L1 inhibitor, to neoadjuvant chemotherapy with nab-paclitaxel and cisplatin (TP) may offer improved outcomes for patients with locally advanced esophageal squamous cell carcinoma (ESCC). The study, conducted across six hospitals in China, explored the safety and efficacy of this combination compared to chemotherapy alone. The results suggest a potential benefit in terms of pathological complete response (pCR) and tumor downstaging.
The trial enrolled 70 patients with ESCC, with 64 patients randomized to receive either socazolimab plus TP or placebo plus TP. Patients in the socazolimab group received 5 mg/kg of the drug intravenously, along with nab-paclitaxel (125 mg/m2) and cisplatin (75 mg/m2) every three weeks for four cycles. All patients underwent video-assisted thoracoscopy esophagectomy after neoadjuvant treatment.
The primary endpoint of the Phase II study was the major pathological response (MPR) rate. Secondary endpoints included R0 resection rate, pCR rate, safety, disease-free survival (DFS), event-free survival (EFS), and overall survival (OS). While the MPR rate was not significantly different between the two groups (69.0% for socazolimab + TP vs. 62.1% for placebo + TP, P = 0.581), a notable difference was observed in the proportion of patients achieving complete regression of the primary tumor (ypT0 stage). The socazolimab + TP group had a significantly higher proportion of patients with ypT0 tumors compared to the placebo + TP group (37.9% vs. 3.5%; P = 0.001).
Pathological Response and Downstaging
The pCR rate, defined as the absence of residual tumor cells, was 41.4% in the socazolimab + TP group compared to 27.6% in the placebo + TP group. This suggests that the addition of socazolimab to chemotherapy may enhance complete tumor regression. Furthermore, the study found that T stage downstaging occurred in 65.5% of patients in the socazolimab + TP group and 62.1% in the placebo + TP group. Notably, T downstaging of Grades 3-4 was observed in 42.1% of patients in the socazolimab + TP group, while no patients in the placebo + TP group experienced this level of downstaging.
Safety and Tolerability
The safety profile of the socazolimab combination was generally manageable. Grade ≥ 3 adverse events occurred in 65.6% of patients in the socazolimab + TP group and 62.5% in the placebo + TP group. The most common adverse events included neutropenia, leukopenia, hypokalemia, anemia, and decreased platelet count. Immune-related adverse events (irAEs) were more frequent in the socazolimab + TP group (25.0%) compared to the placebo + TP group (9.4%).
Circulating Tumor DNA Analysis
The study also explored the potential of circulating tumor DNA (ctDNA) analysis to predict treatment response. ctDNA clearance was observed in 36.8% of patients in the socazolimab + TP group and 22.2% in the placebo + TP group, although this difference was not statistically significant (P = 0.476).
Implications and Future Directions
These findings suggest that socazolimab in combination with nab-paclitaxel and cisplatin may be a promising neoadjuvant strategy for locally advanced ESCC. The observed increase in pCR rate and tumor downstaging warrants further investigation in larger, Phase III trials. The study authors noted that the pCR rate achieved with this chemoimmunotherapy regimen appears numerically higher than those reported in previous Phase III trials of neoadjuvant chemotherapy alone.
While neoadjuvant concurrent chemoradiotherapy followed by surgery remains a primary treatment option for locally advanced ESCC, this study suggests that PD-L1 inhibitors may offer a safe and effective alternative. Further research is needed to determine the optimal treatment modality and to identify patient populations that may benefit most from this approach. Ongoing Phase III trials, such as KEYSTONE-2, are evaluating the role of pembrolizumab in combination with chemotherapy in this setting and may provide further insights into the potential of chemoimmunotherapy for ESCC.
