LBA76 - Anlotinib in combined with anti-PD-L1 antibody Benmelstobart(TQB2450) versus sunitinib in first-line treatment of advanced renal cell carcinoma (RCC): A randomized, open-label, phase III study (ETER100)

Background

Benmelstobart（BMSB, TQB2450）is a humanized monoclonal antibody against PD-L1 and Anlotinib (ALTN) is an anti-angiogenic oral multi-target tyrosine kinase inhibitor. Here, we report the interim analysis results of a randomized, open label, phase 3 trial (NCT04523272) comparing BMSB plus ALTN with sunitinib as first-line treatment for advanced RCC patients (pts).

Methods

Eligible pts had untreated unresectable or metastatic clear cell RCC and were favorable, intermediate or poor risk per IMDC criteria. Pts were randomized in a 1:1 ratio to receive BMSB (1200mg) intravenously once every 3 weeks plus ALTN (12mg) orally once daily (2-week on/1-week off) or sunitinib (50mg) orally once daily (4-week on/2-week off). The primary endpoint was progression-free survival (PFS) assessed by the blinded independent central review per RECIST version 1.1.

Results

A total of 531 pts were randomized: 266 to BMSB + ALTN, 265 to sunitinib. As of Janurary 31, 2024, BMSB + ALTN significantly improved PFS (HR 0.53 [95% CI 0.42-0.67]; P< 0.0001; median 18.96 vs 9.76 mo), and ORR (71.59% vs 25.10%; P< 0.0001) after a median follow-up of 19.52 mo.The median overall survival was not reached in both arms (HR=0.66 [95% CI: 0.48-0.92]). The BMSB + ALTN benefit was observed in all subgroups tested, including all IMDC risk and PD-L1 expression subgroups. The incidence of Grade ≥3 adverse events (AEs) (75.0% vs 74.62%), AEs leading to discontinuation of treatment (12.50% vs 6.44%), fatal AEs (4.92% vs 2.27%) were similar between two arms.

Conclusions

Benmelstobart plus Anlotinib provided superior PFS and ORR compared with sunitinib, and had manageable safety in pts with previously untreated advanced RCC. These results support the use of Benmelstobart plus anlotinib as a new first-line treatment for advanced RCC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Chia-Tai Tianqing Pharmaceutical Group Co Ltd.

Funding

Chia-Tai Tianqing Pharmaceutical Group Co Ltd.

Disclosure

All authors have declared no conflicts of interest.