Anlotinib plus benmelstobart as adjuvant therapy in patients with esophageal squamous cell carcinoma: A phase II clinical trial (ALTER-E005).

459 Background: Surgery represents a primary radical treatment for esophageal cancer, However, the risk of recurrence remains noteworthy after surgical resection, underscoring the need for more effective and tolerable postoperative regimens for esophageal squamous cell carcinoma (ESCC). Benmelstobart, a novel PD-L1 blockade, demonstrated promising antitumor activity when combined with anlotinib, an antiangiogenic agent, in the treatment of various tumors including advanced ESCC (NCT05038813) and biliary tract cancer (NCT03996408). Therefore, ALTER-E005 study aimed to evaluate the efficacy and safety of combining anlotinib with benmelstobart as adjuvant therapy in patients (pts) with ESCC. Methods: This was a single-arm, multi-center phase Ⅱ clinical trial. Thirty pts (≥18 years) with histologically confirmed T1-2N1-3M0 or T3-4NanyM0 ESCC who had undergone radical (R0) resection with no recurrence 6 to 12 weeks after surgery and an ECOG PS ≤ 1 were eligible for enrollment. Enrolled pts received oral anlotinib (12 mg, days 1-14) and intravenous benmelstobart (1200 mg, day 1) every 3 weeks for up to 16 cycles or until disease recurrence. The primary endpoint was disease recurrence free (DFS). while secondary endpoints included safety, 1-year DFS rate, 3-year DFS rate, 1- year overall survival (OS) rate, and 3-year OS rate. Results: As of the data cut-off date (September 20, 2024), a total of 30 patients were enrolled with a median age of 67. Among the 30 surgically resected patients with ESCC, 26 (86.7%) had an ECOG score of 1, and 25 (83.3%) were male. According to the eighth edition of the AJCC Cancer Staging Manual, 9 (30.0%) were classified as stage Ⅱ, and 21 (70.0%) were classified as stage Ⅲ. As of the data cut-off date, the median follow-up time was 8.9 months (95% CI: 7.9-12.3). Four pts experienced disease recurrence, and the median duration of DFS has not yet been reached, with 6-month and 1-year DFS rates of 95.7% (95% CI, 72.9%-99.4%), 84.0% (95% CI, 57.7%-94.6%) respectively. Currently, 13 pts are still undergoing therapy. Out of the total 30 patients, 9 (30%) experienced grade 3 treatment-emergent adverse events (TEAEs). No grade 4 or higher TEAEs were observed. The grade 3 TEAEs included hand-foot syndrome (10.0%), hypertension (3.3%), abnormal liver function (3.3%), immune-related hepatitis (3.3%), pneumonia (3.3%), hyperglycemia (3.3%) Lymphocyte count decreased (3.3%), acute cholecystitis (3.3%) and syncope (3.3%). Conclusions: This study highlighted the promising efficacy and safety preliminarily of combining anlotinib with benmelstobart as adjuvant therapy in patients with ESCC who underwent radical (R0) resection and showed no recurrence 6 to 12 weeks after surgery. Clinical trial information: NCT05252078 .