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CONVERSATIONS IN RENAL CELL CANCER

Conversations in Renal Cell Cancer provides an in-depth look at novel treatments
and new studies. Check in frequently for exclusive video interviews, Q&A’s and
expert commentary on key issues facing clinicians today.



VIDEO: BACTERIAL PRODUCT, CBM588, PLUS IMMUNOTHERAPY IMPROVES CLINICAL OUTCOMES
IN METASTATIC RENAL CELL CARCINOMA

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The bifidogenic live bacterial agent CBM588 when used in combination with
nivolumab and ipilimumab, was shown to improve progression free survival and
response rate in patients with metastatic renal cell carcinoma, according to
results from a phase 1 study recently published in Nature Medicine. 



Sumanta Pal, MD, co-director of the kidney cancer program and medical oncologist
at City of Hope, told MD /alert that the positive results from this phase 1
study will hopefully lead to further research on the role of the gut microbiome
in cancer and how altering the microbiome can have synergistic effects with
current therapies like immune checkpoint inhibitors. 

-- 

What motivated you and your colleagues to study CBM588 in combination with
nivolumab and ipilimumab for patients with metastatic renal cell carcinoma?  

For a long time, I've been very interested in the role of the microbiome in
affecting outcomes with immune therapy. This is really inspired by other groups
that have shown associations between the composition of the gut microbiome and
outcomes of immune based treatments. Recently, I've even been more interested in
seeing how we could manipulate the microbiome to enhance outcomes. That's where
CBM588 comes into play. This is actually a product that's widely available in
Japan and marketed there for general bowel ailments. We decided to use it in our
study, because it seems to have some bifidogenic properties, meaning that when
it's ingested this live bacterial product deposits in the colon and actually
elicits substances that seemed to really increase the rates of butyrate in the
gut and thereby increase Bifidobacterium species. This is the mechanism by which
we think it could potentially enhance outcomes with immunotherapy. 



Can you discuss how the phase 1 study was conducted and what the key findings
were? 

We decided to conduct a randomized phase 1 trial. This is not a common design,
but it's something you can do in a context of small trials, which are powered
towards a biologic endpoint. The primary endpoint in our study was to examine
whether or not we could actually increase the proportion of Bifidobacterium in
the stool of patients who are receiving this live bacterial product. In fact,
our study showed a pretty compelling trend towards increases in Bifidobacterium
levels when you took CBM588. It didn't quite meet statistical significance, but
we found what I thought was quite compelling is that responders seem to have
increases in Bifidobacterium levels. 

The study was really intended to determine whether or not you could increase
Bifidobacterium species within stool. What we thought was just really remarkable
is that we saw amazing benefits in terms of clinical outcome, there was a more
than two-fold increase in response rate in patients that got nivolumab and
ipilimumab with CBM588, versus those that didn't get CBM588. We saw that there
was a profound benefit in progression free survival nearly five-fold longer in
terms of median progression free survival, and again this is a small study, so
it warrants further validation. The signal here was very, very strong. We also
have a lot of rich correlatives reported out in our Nature Medicine paper with a
number of efforts that are dedicated towards understanding the rest of the
microbiome beyond just Bifidobacterium and CBM588 itself. It really shows some
compelling and convincing trends and changes for specific species within the
gut. 



What are some next steps to continue this research? 

Beyond this trial, we really do need confirmation in larger numbers of this
clinical effect that we saw with CBM588. We're working on that fairly
aggressively. We're trying to put together proposals for phase 3 clinical trials
that look at the same concept. I do think that ultimately, it will require
vetting in larger studies to determine whether or not CBM588 has activity in
this clinical context. 



What should your fellow clinicians take away from this study? 

I would take away from this that there is potential that we can really enhance
the microbiome in patients to optimize the impact of immunotherapy. I'm hoping
that this will really spur a body of research that investigates the use of light
bacterial products in patients not just with kidney cancer, but a variety of
immunogenic cancer types. 

-- 

Disclosures: Pal did not declare any financial ties to drugmakers.  

Any views expressed above are the author's own and do not necessarily reflect
the views of MD /alert. This transcript was digitally generated and edited for
clarity.

Photo Credit: Getty Images

 
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