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Bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) compared to the investigator’s choice of sunitinib or cabozantinib in previously untreated advanced renal cell carcinoma (RCC): Results from a phase III randomized study (PIVOT-09)


Checkpoint inhibitor (CPI) combinations improve clinical outcomes for patients (pts) with advanced RCC. BEMPEG is a pegylated IL-2 prodrug, designed with the intent to preferentially bind to IL-2Rβγ. PIVOT-09 is a Phase III, randomized trial of BEMPEG + NIVO vs VEGF-targeted tyrosine kinase inhibitor (TKI) of investigator’s choice for 1L RCC (NCT03729245).


Adult pts with measurable and untreated advanced/metastatic clear-cell RCC were randomized 1:1 (stratified by IMDC risk score and TKI choice) to receive BEMPEG IV 0.006 mg/kg + NIVO IV 360 mg q3w vs sunitinib 50 mg PO qd for 4 weeks followed by 2 weeks off, or cabozantinib 60 mg PO qd. Primary endpoints were objective response rate (ORR) by blinded independent central review (BICR) and overall survival (OS) in pts with IMDC intermediate (I) or poor (P) risk, and in IMDC all-risk disease. The overall study α is 0.05 (2-sided), which is split with 0.001 for ORR and 0.049 for OS.


623 pts (IMDC I/P n=514; IMDC favorable n=109) were randomized and 616 pts (IMDC I/P n=509; IMDC favorable n=107) received ≥1 dose of treatment (sunitinib n=221; cabozantinib n=85). Efficacy results for the IMDC I/P groups are reported. At a median duration of follow-up of 15.5 months, ORR was 23.0% for BEMPEG + NIVO vs 30.6% for the TKI arm. OS in IMDC I/P with p-value of 0.19 did not pass the pre-specified alpha of 0.01 at the interim analysis. mOS was 29.0 months for BEMPEG + NIVO and not reached for the TKI arm (HR=0.82, 99% CI: 0.56-1.21). In IMDC all-risk group, the most common treatment-related adverse events (TRAEs, >20%) of any grade in BEMPEG + NIVO arm were pyrexia (32.6%), pruritus (31.3%), nausea (24.2%), eosinophilia (23.9%), hypothyroidism (22.9%), rash (22.9%), and arthralgia (20.0%). Grade ≥3 TRAEs occurred in 83 pts (26.8%) and 24 pts (7.7%) discontinued due to TRAEs for BEMPEG or NIVO. Grade 5 TRAEs occurred in 3/310 pts (1.0%).


In pts with treatment-naïve advanced/metastatic clear-cell RCC, BEMPEG + NIVO did not improve outcomes vs investigator’s choice of TKI. The combination’s safety profile was consistent with previous reported findings.

Clinical trial identification

NCT03729245; Trial protocol: 17-214-09 / CA045-002 (October 19, 2021).