Anlotinib combined with penpulimab and nab-paclitaxel as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): A single-arm, open-label phase II clinical trial.

367 Background: Recently, PD-1 blockades combined with dual chemotherapy regimens in first-line setting exhibited encouraging efficacy for patients with ESCC. However, the safety profile of conventional dual chemotherapy remained unsatisfactory. Therefore, PD-1 blockades combined with anti-angiogenic tyrosine kinase inhibitors (TKIs) and single chemotherapy regimen might offer a promising strategy. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as first-line combination therapy or second-line monotherapy for ESCC patients in China clinically. Therefore, this study was designed to explore the efficacy and safety of anlotinib combined with penpulimab (PD-1 blockade) and nab-paclitaxel as first-line therapy in advanced ESCC. Methods: Patients with previously untreated metastatic or locally advanced ESCC were recruited and treated with anlotinib (12mg, po, d1~14, q3w) and penpulimab (200mg, iv, d1, q3w) plus nab-paclitaxel (220mg/m 2 , iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 using CT scans every two cycles. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 30. Primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and OS. Results: From Jul 2022 to Sep 2024, a total of 30 patients were enrolled, with 29 patients who had received first tumor response were included in this analysis. The best overall response indicated that there were 1 CR (3.4%), 23 PR (79.3%), 2 SD (6.9%) and 3 NE (10.3%). Therefore, the preliminary ORR was 82.8% (95%CI: 64.2%-94.2%), DCR was 89.7% (95%CI: 72.6%-97.8%). The primary median PFS of the 29 patients was 10.84 months (95%CI: 7.57-14.11). Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-emergent adverse events among the 29 patients with the incidence >20% were anemia (62%), leukopenia (31%), peripheral neurotoxicity (28%) and rash (21%). Common grade ≥3 treatment-emergent adverse events were leukopenia (7%), glutamic-pyruvic transaminase was elevated (3%), glutamic oxalacetic transaminase increased (3%), hypertension (3%), diarrhea (3%) and rash (3%). Conclusions: The combination of anlotinib plus penpulimab and nab-paclitaxel as first-line therapy for advanced ESCC demonstrated promising efficacy and manageable safety profile. And the conclusions needed to be confirmed in subsequent trials. Clinical trial information: ChiCTR2400089133 .