KEY TAKEAWAYS
- The Phase III PIVOT-09 NCT03729245 trial is an open-label, randomized study with 623 participants.
- The study aims to compare the effectiveness and safety of the combination of Bempegaldesleukin (BEMPEG) + nivolumab (NIVO), an IL-2 pro drug and checkpoint inhibitor, respectively.
- The study’s primary outcome measure was ORR and OS in the intermediate- or poor-risk patients and all-risk patients with previously untreated advanced RCC.
- The study found that the combination of BEMPEG + NIVO did not have better outcomes than the TKI of the investigator’s choice.
PIVOT-09 (NCT03729245) is a Phase III, randomized study comparing BEMPEG + NIVO to the investigator’s preferred VEGF-targeted tyrosine kinase inhibitor (TKI) for 1L RCC. Adult patients were randomized 1:1 (based on IMDC risk score and TKI option) 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. The primary endpoints were to be measured by blinded independent central review (BICR) in patients with intermediate (I) or poor (P) risk IMDC illness as well as in IMDC all-risk disease. The two-sided research average is 0.05, divided into 0.001 for ORR and 0.049 for OS.
About 616 patients (IMDC I/P n=509; IMDC favorable n=107) got less than one dose of treatment (sunitinib n=221; cabozantinib n=85) after being randomly assigned among 623 patients (IMDC I/P n=514; IMDC favorable n=109).
At a median follow-up time of 15.5 months, the ORR for BEMPEG + NIVO was 23.0%, while it was 30.6% for the TKI group. With a p-value of 0.19, OS in IMDC I/P failed to meet the intermediate analysis’s pre-specified alpha threshold of 0.01. mOS were not achieved for the TKI arm and were 29.0 months for BEMPEG + NIVO (HR=0.82, 99% CI: 0.56-1.21).
In the IMDC all-risk group, pyrexia, pruritus, nausea, eosinophilia, hypothyroidism, dermatitis, and arthralgia were the most frequent treatment-related adverse events (TRAEs, >20%) of any grade. A total of 83 participants (26.8%) had grade 3 TRAEs, and 24 participants (7.7%) were dropped because of TRAEs for BEMPEG or NIVO. Around 3/310 patients (1.0%) of the total suffered grade 5 TRAEs.
In patients with advanced/metastatic clear-cell RCC who had not received therapy previously, BEMPEG + NIVO had no better results than the TKI of the investigator. The combination’s safety rating matched up with previously published research.
Source:https://oncologypro.esmo.org/meeting-resources/esmo-congress/bempegaldesleukin-bempeg-plus-nivolumab-nivo-compared-to-the-investigator-s-choice-of-sunitinib-or-cabozantinib-in-previously-untreated-advance
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03729245
Tannir, N., Formiga, M.N., Agarwal, N., Pal, S.K., Cho, D., George, D.J., Hong, W., Tang, L., Qureshi, A., Tagliaferri, M.A., Zalevsky, J., Penkov K.D. (2023) LBA68 – 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). Annals of Oncology (2022) 33 (suppl_7): S808-S869. 10.1016/annonc/annonc1089
