Dr Braun on the Clinical Implications of the CONTACT-03 Trial in RCC

David Braun, MD, PhD, assistant professor, medicine (medical oncology), Louis Goodman and Alfred Gilman Yale Scholar, member, Center of Molecular and Cellular Oncology, Yale Cancer Center, discusses the findings from the phase 3 CONTACT-03 trial (NCT04338269) investigating immunotherapy rechallenge in patients with renal cell carcinoma (RCC) and the implications of these findings on the RCC treatment paradigm.

The CONTACT-03 trial randomly assigned patients with RCC with disease progression on or after a prior immune checkpoint inhibitor to receive oral cabozantinib (Cabometyx) at 60 mg once daily with or without intravenous atezolizumab (Tecentriq) at 1200 mg every 3 weeks. At a median follow-up of 15.2 months (interquartile range, 10.7-19.3), 65% and 64% of patients in the combination and monotherapy arms, respectively, had experienced disease progression or died. The median progression-free survival (PFS) was 10.6 months (95% CI, 9.8-12.3) in the combination arm and 10.8 months (95% CI, 10.0-12.5) in the monotherapy arm (HR, 1.03; 95% CI, 0.83-1.28; P = .78).

CONTACT-03 aimed to determine the efficacy of immune checkpoint inhibitor rechallenge in patients previously treated with an immune checkpoint inhibitor, Braun says. One limitation of this trial was the use of the PD-L1 inhibitor atezolizumab, Braun notes. Although PD-L1 inhibitors have clinical activity in patients with kidney cancer, they are likely less effective than standard PD-1 inhibitors, Braun emphasizes.

The findings from CONTACT-03 showed no benefit with the addition of atezolizumab to cabozantinib in any end point, including overall response rate, duration of response, primary progressive disease rate, PFS, and overall survival, rendering this a negative trial. Furthermore, the doublet resulted in a higher rate of treatment-related toxicities than cabozantinib monotherapy. Although the CONTACT-03 trial had limitations, the overall efficacy and safety data indicate that immune checkpoint inhibitor rechallenge should not be routinely used in patients with RCC who have progressed on a prior immune checkpoint inhibitor, Braun concludes.