Dr McGregor on Next Steps For Cabozantinib Plus Atezolizumab in Advanced RCC

Bradley McGregor, MD, senior physician, clinical director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, instructor in medicine, Harvard Medical School, discusses the next steps for investigating cabozantinib (Cabometyx) plus atezolizumab (Tecentriq) in patients with advanced renal cell carcinoma (RCC).

The phase 1/2 COSMIC-021 trial (NCT03170960) initially examined the treatment combination across multiple cohorts of patients with advanced solid tumors, including patients with non–clear cell RCC. Long-term data presented at the 2023 Genitourinary Cancers Symposium revealed that at a median follow-up of 37.2 months, cabozantinib and atezolizumab elicited an objective response rate (ORR) of 31% (95% CI, 16.1%-50.0%) and a disease control rate of 94% (95% CI, 79.2%-99.2%) in patients with non–clear cell RCC.

Earlier data from COSMIC-021 led to the initiation of the ongoing phase 3 CONTACT-03 trial (NCT04338269), which is evaluating cabozantinib plus atezolizumab vs cabozantinib alone in patients with advanced RCC who have received prior treatment with an immune checkpoint inhibitor. Notably, this phase 3 trial is one of the first to include clear cell RCC, as well as patients with non–clear cell RCC, including papillary, chromophobe, and unclassified RCC, McGregor says. Patients with the chromophobe subtype of non–clear cell RCC are also required to have sarcomatoid differentiation.

In the phase 1/2 study, patients with papillary disease had comparable responses vs those clear cell RCC, McGregor expands. CONTACT-03 represents another effort to improve outcomes for patients with RCC with variant histologies, McGregor continues. Various trials in development are aiming to expand the treatment landscape for these patient populations, and investigators are looking forward to the data being read out, McGregor adds.

The COSMIC-021 data and other results observed from other combination therapies have shown that patients with chromophobe RCC do not respond as well to immunotherapy-based regimens, McGregor says, adding that improving outcomes for this subgroup remains an unmet need.

Rather than grouping different histologies under the non–clear cell RCC umbrella, classifying these different groups of patients as a unique subset could help identify more efficacious therapies for these different populations, McGregor concludes