The trial COSMIC-021 is one that actually includes multiple histologies across multiple cohorts
including breast cancer, prostate cancer, colorectal cancer. Specifically at ASCO 2022 we presented
data pertaining to urothelial cancer. The study specifically investigated three cohorts of patients –
patients who were cisplatin eligible, cisplatin ineligible and patients who had received prior immune
checkpoint inhibitors in cohorts 3, 4 and 5 respectively. We assessed the combination of cabozantinib
with atezolizumab; cabozantinib was dosed at 40mg daily, atezolizumab at the conventional dose of
1,200mg intravenous every three weeks. Essentially we used objective response rate as the primary
endpoint of the trial. Each cohort, 3, 4 and 5 had thirty patients a piece.
Ultimately we saw a graded response across the three cohorts. Cohort 3, which included a total of
thirty patients had a response rate of 20%; again that was patients that were cisplatin ineligible.
Cohort 4, patients that were cisplatin eligible, demonstrated a response rate of 30%. Finally, in cohort
5 where we had patients with prior immune checkpoint inhibitor therapy we saw a response rate of
10%. Now, one thing that the response rates may not convey is the duration of response and, in
particular, in cohort 4, cisplatin eligible patients, we saw a very healthy duration of response, in fact,
the median value not yet reached. To me, that’s a signal that that’s a particular place where it may
confer some benefit.
Response rates were measured by the investigator, in this case using RECIST version 1.1. Ultimately
the response rates that we saw in COSMIC-021 were encouraging and I would propose that the next
step is already in play in some respects. There’s a trial that’s ongoing known as the MAIN-CAV study
run by Dr Shilpa Gupta at the Cleveland Clinic; it’s being run through the Alliance Cooperative Group.
The trial looks at the principle of using maintenance avelumab with or without cabozantinib, so a
different immune checkpoint inhibitor but the same principle of combining with a multi-kinase inhibitor,
cabozantinib. That’s going to be the ultimate demonstration of whether or not there’s real synergy
between cabozantinib and atezolizumab.
The toxicity profile associated with cabozantinib with atezolizumab in COSMIC-021 was no different
from what we’ve reported out from other cohorts. In general the standouts for toxicity included fatigue,
increases in AST and ALT and so forth, but in most cases the toxicities were quite manageable.
Importantly, we didn’t see any grade 5 adverse events in the study.