Benmelstobart Combo Elicits PFS Advantage in Untreated Advanced ccRCC

Efficacy data revealed that at a median follow-up of 22.8 months for the interim analysis, 48% of the benmelstobart arm and 21% of the sunitinib arm were still receiving treatment, with the primary reason for discontinuation being disease progression in both arms.

The addition of benmelstobart (TQB2450) to anlotinib (Fukewei) exhibited advantageous progression-free survival (PFS) outcomes vs sunitinib (Sutent) in the treatment of patients who are Chinese with previously untreated advanced clear cell renal cell carcinoma (ccRCC), according to findings from the phase 3 ETER100 trial (NCT04523272) published in The Lancet Oncology.1

Efficacy data revealed that at a median follow-up of 22.8 months (IQR, 15.2-29.7) for the interim analysis, 48% of the benmelstobart arm and 21% of the sunitinib arm were still receiving treatment, with the primary reason for discontinuation being disease progression in both arms. Additionally, disease progression per blinded independent review committee (BIRC) or death occurred in 48% vs 55% of the respective arms. The median PFS was 19.0 months (95% CI, 15.3-22.8) vs 9.8 months (95% CI, 8.4-12.4), respectively (HR, 0.53; 95% CI, 0.42-0.67; P <.0001).

In a per-protocol set, the median BIRC-assessed median PFS was 19.0 months (95% CI, 16.5-22.8) vs 11.0 months (95% CI, 8.5-13.6) in the combination and control arms, respectively (HR, 0.55; 95% CI, 0.43-0.70; P < .0001). The between-group difference met the prespecified threshold for significance (P = .0153). Additionally, the Kaplan-Meier estimates for PFS at 12 months were 65% (95% CI, 59%-71%) in the combination arm vs 44% (95% CI, 37%-51%) in the control arm; a post hoc analysis of 24-month PFS showed values of 42% (95% CI, 34%-49%) vs 26% (95% CI, 18%-33%).

Subgroup analyses generally favored the benmelstobart combination vs sunitinib, including patients with intermediate-poor International Metastatic RCC Database Consortium (IMDC) risk as well as those with a PD-L1 combined positive score (CPS) of less than 1. Overall survival (OS) data were not mature as of the interim analysis, and 24% vs 30% of patients in each arm had died as of data cut off, mostly due to disease progression.

“The ETER100 trial showed that benmelstobart plus anlotinib resulted in a significant [PFS] benefit and higher objective response rate [ORR] compared with sunitinib in the first-line treatment of advanced [ccRCC],” Aiping Zhou, MD, a professor from the Department of Medical Oncology at the National Cancer Center/Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China, wrote in the publication with study coinvestigators. “The safety profile of this combination was manageable without new safety signals. These findings support the use of benmelstobart plus anlotinib as an effective and safe therapeutic option for patients with advanced [ccRCC].”

Patients 18 years to 80 years old who are Chinese with previously untreated histologically confirmed advanced ccRCC in the open-label phase 3 trial were randomly assigned 1:1 to received benmelstobart plus anlotinib (n = 264) or sunitinib (n = 263). Treatment in the combination arm consisted of 1200 mg of benmelstobart on day 1 of 3-week cycles and anlotinib given orally at 12 mg daily for the first 2 weeks of each cycle. Those in the control arm received 50 mg of daily sunitinib for the first 4 weeks of 6-week cycles.

Across the investigational and control arms, the median age was 60 years (IQR, 54-67) vs 59 years (IQR, 54-67), with 64% and 69% of each arm being younger than 65 years. Most patients in either arm were male (77% vs 75%), Han (94% vs 94%), and had an ECOG performance score of 1 (73% vs 74%). Additionally, patients most commonly had an intermediate IMDC prognostic risk (71% vs 72%), lung metastases (63% vs 61%), and a PD-L1 CPS of less than 1 (73% vs 72%).

The primary end point of the trial was BIRC-assessed PFS. Secondary end points included investigator-assessed PFS, OS, and ORR assessed by BIRC and investigators.

Per BIRC assessment, the ORR was 72% (95% CI, 66%-77%) with the benmelstobart combination vs 25% (95% CI, 20%-31%) with sunitinib (P <.0001), with a median duration of response (DOR) of 17.9 months (95% CI, 13.7-29.4) vs 16.3 months (95% CI, 10.7-24.5). Based on investigator evaluation, the ORR was 68% (95% CI, 62%-74%) vs 25% (95% CI, 20%-30%) in each arm (P <.0001); the median DOR was 16.8 months (95%CI, 13.9-26.3) vs 16.6 months (95% CI, 8.3-28.8), respectively.

In the safety population, the median duration of treatment in the combination arm was 20 cycles for benmelstobart and anlotinib (IQR; 12-28 and 12-30) vs 6 cycles (IQR, 2-10) for sunitinib. Additionally, the median time to first dose interruption or reduction was 19 weeks, 20 weeks, and 7 weeks, respectively.

Any-grade treatment-emergent adverse effects (TEAEs) occurred in 99% vs 99% of the investigational and control arms, with 75% vs 75% experiencing grade 3 or higher TEAEs. Furthermore, treatment-related AEs (TRAEs) occurred in 98% of each arm, with grade 3 or higher TRAEs occurring in 67% vs 66% of each arm.Common grade 3 or higher TRAEs were hypertension (34% vs 21%), platelet count decreases (1% vs 23%), neutrophil count decreases (2% vs 16%), white blood cell count decreases (1% vs 11%), and anemia (1% vs 9%).

Deaths due to treatment occurred in 3 patients in the combination arm due to cardiac-respiratory arrest, renal failure, and an unknown cause. Health-related quality of life data, particularly changes FKSI-15 scores compared with baseline, indicated more favorable outcomes with the benmelstobart-based combination vs sunitinib.

Reference

Zhou A, Shen P, Li J, et al.First-line benmelstobart plus anlotinib versus sunitinib in advanced renal cell carcinoma (ETER100): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2025;26(9):1145-1157. doi:10.1016/S1470-2045(25)00343-2