Camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (ESCC): A single-arm, phase II trial

4048 Background: This study (NCT05476380) aimed to evaluate the safety and efficacy of neoadjuvant camrelizumab plus chemotherapy in patients with locally advanced ESCC, and to explore the potential risk factors of tumor immune microenvironment (TIM) which affect the efficiency of immunotherapy. Methods: Patients with resectable locally advanced thoracic ESCC, staged as T1b-4a, N2-3 (≥3 stations), and M0 or M1 lymph node metastasis (confined to supraclavicular lymph nodes) were enrolled. Eligible patients received intravenous camrelizumab (200 mg, day 2) plus paclitaxel (175 mg/m 2 , day 1) and cisplatin (75 mg/m 2 , day 1) for three 21-day cycles before surgery. The primary endpoint was major pathological response (MPR), defined as ≤10% residual viable tumor cells in resected tissue. In order to screen out the potential biomarkers, the dissected lymph nodes were collected in the pathological complete response (pCR) and non-pCR groups. The infiltrated immune cells and the status of PD-L1 was evaluated by flowcytometry. Results: From February 20, 2021 to July 7, 2022, 38 patients were enrolled. 34 (89.5%) patients completed the full three-cycle treatment successfully. 34 patients underwent surgery and all received R0 resection. The MPR and pCR rates were 67.6% (23/34) and 17.6% (6/34), respectively. There were 2 (5.9%) patients having complete response of the primary tumor but residual disease in lymph nodes alone (ypT0N+). 32 (94.1%) patients had any-grade treatment-related adverse events, with the most common being leukocytopenia (73.5%). 18 (52.9%) patients had adverse events of grade 3 or worse. No treatment-related deaths occurred. Based on our findings, positive lymph nodes were one of the important reasons that the patients could not achieved pCR. TIM of the lymph nodes were then tested. Compared with MPR group, the infiltrated lymphocyte cells in the non-MPR group decreased from 93% to 52.4% (p = 0.02), the infiltrated CD8 + T cells also decreased from 11.8% to 5.9% (p = 0.02). However, the CD4 + T cells showed no significant difference between the MPR and non-MPR groups (46.2% vs 55%, p = 0.27). The expression of PD-L1 in the immune cells is one of the biomarkers for checkpoint inhibitors. In this trial, the expression of PD-L1 in the CD8 + T cells showed significant difference between the MPR and non-MPR groups (14.5% vs 6.7%, p = 0.02). Myeloid-derived suppressor cells (MDSCs) are a group of vastly heterogeneous immunosuppressive cells derived from immature myeloid progenitors that have been linked to poor patient prognosis and immunosuppression. We found more infiltrations of MDSCs in the non-MPR group compared with the MPR group (9.7% vs 4.7%, p = 0.04). Conclusions: Neoadjuvant camrelizumab combined with chemotherapy shows promising efficacy and good safety in ESCC patients. Poor response to immunotherapy was related to lymph node metastasis in the TIM. Clinical trial information: NCT05476380 .