CBM588 With Cabozantinib/Nivolumab Shows Promise in Metastatic RCC
Hedyeh Ebrahimi, MD, MPH, discusses updated data from a phase 1 study of CBM588, cabozantinib, and nivolumab in metastatic renal cell carcinoma.
Hedyeh Ebrahimi, MD, MPH, of City of Hope Comprehensive Cancer Center in Duarte, California, discusses updated data from a phase 1 study (NCT05122546) of CBM588 plus cabozantinib (Cabometyx) and nivolumab (Opdivo) in metastatic renal cell carcinoma (mRCC).1
Presented at the 2025 Genitourinary Cancers Symposium, data from the phase 1 indicate that the addition of CBM588 to cabozantinib and nivolumab significantly improved progression-free survival (PFS) and objective response rate (ORR) in patients with mRCC.1 However, the study did not demonstrate a significant increase in Bifidobacterium spp., the primary end point, challenging initial hypotheses regarding the mechanism of action.
Ebrahimi and colleagues conducted a single-center, randomized, open-label, investigator-initiated phase 1 trial (NCT05122546) involving treatment-naive patients with mRCC with clear cell, papillary, or sarcomatoid components. Patients were randomized 2:1 to receive cabozantinib (40 mg daily) plus nivolumab (480 mg every 4 weeks), with or without CBM588 (80 mg twice daily).
Enrollment was open to patients with an ECOG performance status of 0 or 1 who had not previously received systemic treatment for metastatic disease. Patients must not have had active autoimmune disease and must not have been receiving high-dose steroids.2
“This study is aiming to understand if adding CBM588, a live bacterial product, to a standard regimen of cabozantinib plus nivolumab will have any added clinical benefit for our patients or not,” explains Ebrahimi.
References
Ebrahimi H, Meza LA, Dizman N, et al. Cabozantinib and nivolumab with or without CBM588 in patients with metastatic renal cell carcinoma: Updated clinical outcomes of a phase I study. J Clin Oncol. 2025;43(suppl 5):543. doi:10.1200/JCO.2025.43.5_suppl.543
Ebrahimi H, Dizman N, Meza L, et al. Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nat Med. 2024;30(9):2576-2585. doi:10.1038/s41591-024-03086-4
