ETER901: A randomized, open-label, phase III trial of anlotinib in combination with anti-PD-L1 antibody benmelstobart (TQB2450) versus nab-paclitaxel in first-line treatment of recurrent or metastatic triple-negative breast cancer.

1104Background: Recurrent or metastatic triple-negative breast cancer (TNBC) represents an aggressive malignancy with unfavorable prognoses. Benmelstobart (TQB2450) is a humanized monoclonal antibody targeting PD-L1, and anlotinib (ALTN) is an anti-angiogenic oral multi-target tyrosine kinase inhibitor. Herein, we present the findings of a randomized, open-label, phase 3 study comparing the combination of benmelstobart plus ALTN with nab-paclitaxel as first-line treatments for patients (pts) with recurrent or metastatic TNBC. Methods: In this phase 3 trial, patients with previously untreated stage IV or recurrent/metastatic TNBC were randomly allocated in a 1:1 ratio. One group received 1200 mg of intravenous benmelstobart on day 1, along with 12 mg of oral ALTN from days 1 to 14, following a 3-week cycle. The other group was administered 100 mg/m² of intravenous nab-paclitaxel on days 1, 8, and 15 within a 4-week cycle. Randomization was stratified based on whether patients had received neoadjuvant or adjuvant taxane therapy and the presence or absence of liver or brain metastases at baseline. The primary endpoint was progression-free survival (PFS), evaluated by the blinded independent central review by RECIST version 1.1. Results: The initial plan was to enroll 332 pts in this trial. However, due to the COVID-19 pandemic, the enrollment process was delayed, and recruitment was terminated in January 2023. Eventually, 147 pts were randomized (with a median follow-up of 14 months), among whom 75 were assigned to the benmelstobart plus ALTN group and 72 to the nab-paclitaxel group. In the intention-to-treat analysis, as assessed by the investigators, the median PFS was 7.85 months for the benmelstobart plus ALTN combination, in contrast to 5.55 months for nab-paclitaxel (hazard ratio, 0.70; 95% confidence interval, 0.46 to 1.06; P = 0.1687). The median overall survival was 35.81 months for study group and 21.03 months for control group (hazard ratio, 0.78; 95% confidence interval, 0.49 to 1.24; P = 0.2625). Grade ≥3 drug-related adverse events occurred in 56.5% of the patients in the study group and 36.6% in the control group. The most prevalent grade ≥3 adverse events in the study group were hypertension (28.0%) and hypertriglyceridemia (13.3%). Conclusions: The combination of benmelstobart plus ALNT might extend both progression-free survival and overall survival in the first-line treatment of patients with recurrent or metastatic TNBC. The adverse events were in line with the previously established safety profiles of each individual agent. (Funded by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. ClinicalTrials.gov number, NCT04405505). Clinical trial information: NCT04405505.