Dr Gupta on the MAIN-CAV Trial of Maintenance Cabozantinib Plus Avelumab in mUC

Shilpa Gupta, MD, director, Genitourinary Medical Oncology, Taussig Cancer Institute, co-leader, Genitourinary Oncology Program, Cleveland Clinic, discusses the design, methodology, and potential significance of the ongoing phase 3 MAIN-CAV trial (NCT05092958) in patients with locally advanced/metastatic urothelial carcinoma.

This randomized, multicenter, international trial will assess the efficacy and safety of maintenance cabozantinib (Cabometyx) plus avelumab (Bavencio) vs maintenance avelumab alone, Gupta begins. A total of 654 patients with metastatic urothelial carcinoma who did not experience disease progression after 4 to 6 cycles of prior platinum-based chemotherapy will be enrolled on the trial, she states.

These patients will be randomized 1:1 to either the combination or avelumab monotherapy within 3 to 10 weeks after their last dose of chemotherapy, Gupta continues. The primary end point is overall survival (OS). Key secondary end points are progression-free survival, safety, tumor response, and health-related quality of life, she adds. Correlatives to assess biomarkers of response and avelumab resistance include tissue, blood, circulating tumor DNA, and urine analysis.

The MAIN-CAV study builds upon previous level 1 evidence for first-line avelumab maintenance therapy from the phase 3 JAVELIN Bladder 100 trial (NCT02603432), Gupta explains. This pivotal trial demonstrated that the addition of avelumab maintenance to best supportive care significantly improved OS vs best supportive care alone, she says. These data solidified switch maintenance with avelumab as the standard of care in this space, and accordingly led to the FDA approval of maintenance avelumab for patients with locally advanced or metastatic urothelial cancer who have not progressed on prior platinum-based chemotherapy.

Importantly, patients in JAVELIN Bladder 100 who had visceral metastases derived less benefit from avelumab maintenance compared with those who did not have visceral metastases, Gupta notes. It was hypothesized that the addition of a non-cross resistant therapy with non-overlapping toxicity would not only show synergy, but increase benefit without decreasing safety for this patient population, she details. Based on its previous efficacy in combination with immune checkpoint inhibitors in platinum-refractory metastatic urothelial cancer, cabozantinib was selected, Gupta says.

The MAIN-CAV trial is currently enrolling in the US and Canada.