First-line TQB2450 plus anlotinib combined with paclitaxel and cisplatin for advanced esophageal squamous cell carcinoma (ESCC): Update results of a multicenter phase II trial.

e16011 Background: PD-1 inhibitor combined with chemotherapy are the standard first-line treatment for advanced ESCC. Anlotinib, a multitargeted tyrosine kinase inhibitor (TKI), has been demonstrated favorable efficacy and manageable toxicity as both first-line treatment when combined with TP and second-line monotherapy in advanced ESCC. TQB2450 is a novel humanized anti-PD-L1 monoclonal antibody. We conducted a phase II trial to evaluate the efficacy and safety of alotinib combined with TQB2450, cisplatin, and paclitaxel as first-line treatment for advanced ESCC. Here is the update results. Methods: Eligible patients (pts) with previously untreated unresectable locally advanced or metastatic ESCC received TQB2450 (1200mg, iv, d1, q3w) plus anlotinib (10mg, po, d1~14, q3w) combined with paclitaxel (135mg/m 2 , iv, d1, q3w) and cisplatin (60~75mg/m 2 , iv, d1~3, q3w) for 4 - 6 cycles as initial therapy. Patients without progressive disease (PD) continued to receive same dose of anlotinib plus TQB2450 as maintenance therapy until PD or unacceptable toxicity. The primary endpoint was PFS (RECIST version 1.1). Secondary endpoints included iPFS (iRECIST), ORR (RECIST version 1.1), DCR, DOR and safety. Results: At the data cutoff date of November 14, 2023, 50 pts were enrolled with a median age of 64 years (range 41-74), male (39/50, 78%) and ECOG PS 1 (38/50, 76%). Among 43 tumor response evaluable pts , 4 achieved complete response, 32 had partial response and 8 had stable disease. The ORR was 72.00% (95% CI: 57.51, 83.77) and the DCR was 84.0% (95% CI: 70.89, 92.83). The 12-month PFS rate was 66.84% (95% CI: 48.73, 79.79) and the 12-month OS rate was 74.22% (95% CI: 59.06, 84.46), but the median PFS and OS was not reached. The incidence of ≥G3 treatment emergent adverse events was 78%, mainly included neutropenia (44%, 22/50), leukopenia (24%, 12/50) and hypertension (20%, 10/50). 20 pts (48%, 24/50) occurred serious AEs. Conclusions: The combination of TQB2450 plus anlotinib, paclitaxel and cisplatin, demonstrated encouraging efficacy and manageable toxicity in patients with advanced ESCC when used as first-line treatment. Clinical trial information: NCT05013697 .