A novel CXCR4 inhibitor for RCC and a novel immunotherapy endpoint | David McDermott

A novel CXCR4 inhibitor for RCC and a novel immunotherapy endpoint | David McDermott


[MUSIC PLAYING] So my name is David McDermott. I’m a medical oncologist in
Boston at Beth Israel Deaconess Medical Center, and I focus
on treating kidney cancer and melanoma. At this meeting, we were
focused on a new target in kidney cancer called
CXCR4, which we believe is involved in resistance to
both angiogenesis inhibition and immune therapy, potentially. So we presented a
trial, a Phase II trial, single-arm trial
of axitinib, which is a standard therapy
for kidney cancer, with this new agent mavorixafor,
which is an inhibitor of CXCR4. We believe CXCR4 is
important because we believe it’s important in allowing cells
like myeloid-derived suppressor cells and T-regulatory cells
to track into the tumor where they generate resistance
to both– they support resistance to both angiogenesis
inhibition and immune therapy. So in this trial, adding
this drug to axitinib produced some
encouraging results. So for example, we saw a
very good tolerability, meaning the side effects
we saw were mostly driven by the axitinib. We saw some encouraging
early signs of efficacy in about 60 patients. We saw a
progression-free survival for the entire group of
about 7.4 months, which is better than the
historical number you’d see with axitinib
alone of just 4.8 months. Obviously, we need to confirm
that in a randomized trial. But the drug is
interesting and it may also be able to be combined
with PD-1 blockades. So as part of this study,
we had a small cohort with combined with nivolumab. So now this agent has been
combined with both PD-1 and with VEGF with some
interesting results. So it’s one of the few
drugs in development that’s been combined with both
sides of the current standard of care for patients with
metastatic kidney cancer. One of those standards
is PD-1/VEGF. So you could imagine a
drug like this potentially being added to a triplet
combination in the future, as well as doing randomized
trials in patients who are just receiving VEGF alone. So we’re excited about
that going forward. More studies are
needed, obviously. The other thing that we
talked about at this meeting was a novel endpoint for
immune therapy trials, this what we’re terming
treatment-free survival, which is a way of looking at
overall survival of patients on therapy and off therapy
and on subsequent therapy. It’s a way of sort of
breaking down survival, the different
stages people would be in while they’re alive. They can either be
alive on treatment, they can be alive on
subsequent treatment. But with immune therapy,
one of the exciting aspects of immune therapy is you can be
alive off treatment and living in remission of your disease. So treatment-free survival is a
way of measuring that outcome. But not just looking
at the positives, not just looking at the
treatment-free intervals people get, but also the toxicity that
may persist during that period, because both the positive
effects of immune therapy can last for months, and, in
some patients, years, but also, side effects can last, too. So we were showing both toxicity
and benefit during this period. And we looked at it in
the CheckMate 214 study, which was the pivotal trial that
led to ipilimumab and nivolumab being approved for use. And there we saw much more
treatment-free survival in the patients getting
IO therapy than sunitinib without a subsequent
increase in side effects. So this might be a way of– additional way– on top of
progression-free survival and overall survival, about
measuring the true value of immune therapy in patients
getting combination regimens in the future. We published this data
two weeks ago in melanoma. This was the first
look in kidney cancer. And we hope to look at
it in other tumor types, like lung cancer,
in the near future. [MUSIC PLAYING]

Leave a Reply

Your email address will not be published. Required fields are marked *