Benmelstobart (TQB2450) combined with anlotinib hydrochloride capsule in the treatment of advanced, recurrent, or metastatic endometrial cancer: A multicohort, open label, multicenter, phase II clinical trial (TQB2450-II-08).

Background: The treatment options after first-line chemotherapy for endometrial cancer (EC) are very limited. Several immune checkpoint inhibitors or combined with antiangiogenic drugs have shown antitumor activity and been approved in EC. Anlotinib is a multiple-targeted tyrosine kinase inhibitor that has been approved for the treatment of several solid tumors. Benmelstobart (TQB2450) is a humanized monoclonal antibody targeting programmed death-ligand 1 (PD-L1). This multicohort, open label, multicenter, phase II study aims to evaluate the efficacy and safety of TQB2450 injection or combined with anlotinib hydrochloride capsule in the treatment of recurrent or metastatic advanced EC. Methods: Patients with pathologically confirmed recurrent or metastatic advanced EC failed at 1 or 2 prior lines of therapy will be enrolled. Non-MSI-H/dMMR patients were treated with TQB2450+anlotinib therapy (TQB2450 1200mg, IV D1/Q3W; anlotinib 12mg PO QD, D1-14/Q3W) (cohort 1) or anlotinib (cohort 3), MSI-H/dMMR patients were treated with TQB2450 (cohort 2), until disease progression or intolerable toxicity experienced. Cohort 1 is divided into two stages for enrollment. In the first stage, 22 patients are enrolled. If the lower limit of the confidence interval is greater than 15%, indicating that there are at least 8 patients achieved CR/PR, consideration can be given to proceeding to the next stage. In the second stage, 85 patients are enrolled. The primary endpoint was the objective response rate (ORR) by independent review committee (IRC). Key secondary endpoints include ORR by investigator, disease control rate (DCR), duration of response (DoR), progression free survival (PFS), overall survival (OS) and safety. Results: As of November 09, 2023, 170 patients were enrolled and treated (cohort 1 N=107, cohort 2 N=32, cohort 3 N=31). In the first stage, 22 patients enrolled, 8 achieved CR/PR, and the study progressed to the second stage in cohort 1. Antitumor activities are shown in the table. Treatment-emergent adverse events (TEAEs) occurred in 99.07%, 100% and 100% of patients. Grade ≥3 TEAEs were reported in 74.77%, 40.63% and 87.10% of patients, respectively, with the most common ones being weight loss (46.73%, 25%, 29.03%), white blood cell decreased(47.66%, 12.5%, 19.35%), blood corticotrophin increased (44.86%, 15.63%, 22.58%), thyroid stimulating hormone increased (37.38%, 3.13%, 25.81%). Conclusions: TQB2450 plus anlotinib showed promising antitumor activity with a manageable safety profile in the treatment of recurrent or metastatic advanced EC. Clinical trial information: NCT04574284. (Table presented.)