Neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma with camrelizumab, albumin-paclitaxel, carboplatin and apatinib (GASTO-1093): A single-arm, open-label, phase 2 trial

e16068 Background: Camrelizumab combined with chemotherapy has shown antitumor efficacy in the neoadjuvant therapy of esophageal squamous cell carcinoma (ESCC). Apatinib, a selective inhibitor of VEGFR2, showed a synergistic effect when combined with camrelizumab and chemotherapy in advanced ESCC. We aim to assess the efficacy and safety of using the combination of camrelizumab with apatinib and chemotherapy (albumin-paclitaxel plus carboplatin) as the neoadjuvant therapy for ESCC. Methods: Patients with untreated, resectable (stage II or III) ESCC were enrolled. Each patient received two 21-day cycles of neoadjuvant treatment with intravenous camrelizumab (200mg), albumin-paclitaxel (260mg/m 2 ), carboplatin (area under the curve = 5) on day 1, and oral apatinib 250 mg/day on days 1-14, followed by the third cycle without apatinib. The patients underwent surgical resections about 9 weeks after Day 1 of Cycle 1. The primary end point was pathological complete response (PCR). Secondary endpoints included safety, objective response rate (ORR) and disease control rate (DCR). This analysis was approved by the study's Data and Safety Monitoring Committee. Results: Between February 2022 and January 2023, 38 eligible patients were enrolled. Two patients withdrew and eight recent patients have not completed two treatment cycles yet; therefore, 28 patients who have completed the full three-cycle treatment were included in this analysis. The ORR and DCR were 92.9% and 100%, respectively. 26 (92.9%) patients underwent surgery, and R0 resection was achieved in all cases. PCR (ypT0N0) was identified in 11 (42.3%) patients, and 2 (7.7%) patients had complete response of the primary tumor but residual disease in lymph nodes alone (ypT0N+). The most common grade 1 or 2 treatment-related adverse events (trAEs) were pruritus (85.7%), asthenia (75%), and peripheral sensory neuropathy (60.7%). Grade 3 or 4 trAEs included neutropenia (53.6%), leukopenia (53.6%), thrombocytopenia (25%), hepatitis (10.7%), febrile neutropenia (10.7%), hypertension (7.1%), and rash (3.6%). Immune-related AEs included rash (21.4%), hepatitis (10.7%), reactive capillary hemangiomas (10.7%) and hyperthyroidism (3.6%). Of note, treatment-related hepatitis led to the discontinuation of treatment and surgical delay in 1 patient (3.6%). There was no treatment-related, in-hospital, postoperative 30-day, and postoperative 90-day mortality. Conclusions: Neoadjuvant camrelizumab combined with apatinib and chemotherapy in patients with resectable ESCC had manageable trAEs and a high PCR rate (42.3%). Larger cohorts are needed to examine whether this PCR rate is significantly higher than the PCR rate (25%) of a different trial using camrelizumab combined with chemotherapy ( ChiCTR2000028900 ). Clinical trial information: ChiCTR2100051763 .