Neoadjuvant adebrelimab plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma: A phase 2 trial.

443 Background: Several clinical trials have demonstrated the enhanced pathological response with the addition of immune checkpoint inhibitor to neoadjuvant chemotherapy in patients with resectable esophageal squamous cell carcinoma (ESCC), including the phase 3 ESCORT-NEO trial. Adebrelimab, an anti-programmed cell death-ligand 1 antibody, has shown potential as neoadjuvant monotherapy in the phase 1b NATION-1907 trial of resectable ESCC, with a 2-year overall survival rate of 92% in 30 patients. This study evaluated the efficacy and safety of adebrelimab plus chemotherapy as neoadjuvant therapy in patients with resectable locally advanced ESCC. Methods: In this single-center phase 2 trial (NCT06178211), patients aged 18-75 years with stage II-III (cT2N1-2M0 or cT3N0-2M0) ESCC received adebrelimab (1200 mg, day 1) plus albumin-bound paclitaxel (100 mg/m 2 , days 1, 8, and 15) and carboplatin (area under the curve of 5 mg/mL/min, day 1) every 3 weeks for 2 cycles. Esophagectomy was performed 4-6 weeks after neoadjuvant therapy. The primary endpoint was pathological complete response (pCR; ypT0N0) rate. Secondary endpoints were clinical complete response (cCR) rate (defined as no residual tumor after neoadjuvant therapy, based on computed tomography, positron emission tomography-computed tomography [PET-CT], endoscopic biopsy, and endoscopic ultrasound-guided fine-needle aspiration [EUS-FNA]), margin-free (R0) resection rate, major pathological response (MPR; ≤10% residual tumor cells) rate, event-free survival, overall survival, and safety. Results: Between January 2024 and May 2024, a total of 36 patients were enrolled. Most patients (75.0%) had clinical stage III ESCC. Thirty-five patients completed 2 cycles of neoadjuvant therapy, while one patient refused the last dose of albumin-bound paclitaxel. Two patients refused surgery while 34 underwent esophagectomy. The pCR rate was 38.9% (95% confidence interval [CI], 23.1-56.5) in all patients and 41.2% (95% CI, 24.6-59.3) in the surgery set; the R0 resection rate was 94.4% (95% CI, 81.3-99.3) and 100% (95% CI, 89.7-100), and the MPR rate was 63.9% (95% CI, 46.2-79.2) and 67.6% (95% CI, 49.5-82.6), respectively. The cCR rate was 47.2% (95% CI, 30.4-64.5) in all patients. Of 36 patients, grade ≥3 treatment-emergent adverse events during neoadjuvant therapy included decreased neutrophil count (2 [5.6%]), decreased white blood cell (2 [5.6%]), decreased platelet count (1 [2.8%]), impaired hearing (1 [2.8%]), hyponatremia (1 [2.8%]), immune-mediated hepatitis (1 [2.8%]), intestinal obstruction (1 [2.8%]), and esophageal ulcer (1 [2.8%]). Surgical complications occurred in 17 (50%) of 34 patients. Conclusions: Neoadjuvant adebrelimab plus chemotherapy shows promising pathological response and favorable safety profile in patients with resectable locally advanced ESCC. Survival follow-up is ongoing. Clinical trial information: NCT06178211 .