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Medicine Matters oncology

This year, at GU ASCO 2021, I wanted to highlight my phase 1 plus expansion cohort study of cabozantinib plus nivolumab and cabozantinib, nivolumab plus ipilimumab in multiple genitourinary tumors. So I wanted to give a little bit of background. Preclinical work done at the NCI with cabozantinib in urothelial cancer cell lines and tumors, xenograft mice demonstrated that the MET/HGF pathway, which is targeted by cabozantinib, may be important in urothelial carcinoma and other GU tumors.



So this was my rationale for initiating a phase 2 study of monotherapy cabozantinib in patients with refractory to chemotherapy urothelial carcinoma. And the overall response rate of the study was 19%, and in correlative studies we saw that cabozantinib has immunomodulatory properties with peripheral immune subsets. And this was a rationale for combining cabozantinib with nivolumab and cabozantinib with nivolumab and ipilimumab.



And this is how we developed our phase 1 trial, which was done in multiple GU tumors. The phase 1 trial, the dose escalation phase 1 trial in the initial 54 patients, has been reported, and the outcome shows that the combination of the doublet and the triplet is very active in multiple GU tumors.



And based on the phase 1 trial, we did several expansion cohorts, and here at GU ASCO 2021 we present the pooled analysis of the phase 1 trial, first 54 patients, and the seven expansion cohorts, for a total of a hundred and 20 patients. And we saw that in this very heterogeneous group of patients of multiple different tumor types, the overall response rate was 38%, with a complete response rate of 11%. And the durability of response was 23 months, and the time to response was two months.



And when we look at it by tumor type in kidney cell and renal cell carcinoma, the overall response rate was 63% and included sarcomatoid patients. And the overall response rate in urothelial carcinoma patients was 42%, with a complete response rate of 21%. And we also saw activity in multiple rare GU tumors, including adenocarcinoma of the bladder, urechal tumors, squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, penile cancer, among others.



And the safety and preliminary activity that we saw in this phase 1 trial informed several phase 3 trials in kidney cancer, including the CheckMate-9ER study, the COSMIC-313 study, the Alliance PDIGREE trial, all in renal cell carcinoma in the first-line setting, and also informed our Alliance ICONIC phase 2 trial for rare gene tumors that's currently enrolling.