The trial I’m running right now is to look at the combination of nivolumab, ipilimumab and cabozantinib in renal cell carcinoma patients with brain metastasis. The rationale for this trial is traditionally for renal cell carcinoma patients with brain metastasis the treatment options are pretty much radiation or surgery. We don’t know the exact role of systemic therapy in the treatment of brain metastases from renal cell carcinoma. That’s why we wanted to look at the role of systemic therapy in renal cell carcinoma patients with brain metastasis.

Can you describe the design of the phase II trial and the key eligibility criteria?

This is a phase II trial, it’s a single arm. We plan to enrol a total of 20 patients, so these patients will be metastatic renal cell carcinoma with brain metastasis, treatment naïve ideally. So the patients will receive nivolumab/ipilimumab for a total of four doses in addition to daily cabozantinib. After four doses of nivolumab and ipilimumab we will drop ipilimumab so patients will remain on nivolumab IV infusion and cabozantinib daily until disease progression or patient withdrawal or unacceptable toxicity.

What were the key findings in terms of intracranial and systemic response rates?

The primary endpoints for this trial are intracranial safety and intracranial response. Secondary endpoints are systemic response, systemic progression free survival and overall survival.

So in terms of safety we did not find significant intracranial toxicity from this combination. In terms of efficacy we actually observed a very impressive intracranial response. So, so far, we enrolled 11 patients on this trial, four out of 11 patients actually had a complete response in the brain. This has not been reported before with a combination of immunotherapy and a TKI.

How might these results influence treatment strategies for RCC patients with brain metastases?

That’s a great question. As I mentioned before, standard treatment options for patients with renal cell carcinoma and brain metastasis include either whole brain radiation, GammaKnife or surgery. So typically if the size of the tumour is above 3cm they may have to go for surgery, below that they will go for GammaKnife and if there are too many brain metastases for the radiation oncologist to do GammaKnife then it will be radiation, whole brain radiation. It’s kind of toxic.

So the results from this trial basically provide additional treatment options. So it indicates that systemic therapy can work on brain metastasis from renal cell carcinoma, despite the blood-brain barrier.

Is there anything else you would like to add?

Yes, as I said, the results from this trial basically provide additional treatment options for patients with renal cell carcinoma and brain metastasis. It can potentially change clinical practice. Additionally, we are collecting blood specimens, CSF, which is cerebrospinal fluid, specimens while trying to identify biomarkers that can predict prognosis and response to the treatment.