Sumanta Pal, Professor and Vice Chair of Academic Affairs, City of Hope, shared on LinkedIn:
“One of my proudest career moments to date happened this weekend – wanted to share the path towards getting there.
In May of 2019, I met with the team at Xencor – at the time, they were based in Monrovia, California – just a stone’s throw away from City of Hope. I discussed the existing kidney cancer treatment landscape, and we discussed where we might position a new agent they were developing.
Fast forward a couple of years – we were the first site to open their first-in-human study exploring XMab819, an ENPP3 x CD3 bispecific. We enrolled the first patient and along the way brought on a team of terrific investigators (including but not limited to Randy Sweis, Ritesh Kotecha, Laurence Albiges, Scott Tykodi, Adanma Ayanambakkam, David Braun, David VanderWeele, Shuchi Gulati, Claud Grigg, Christopher Hoimes, Benjamin Garmezy, and Karie Runcie).
Now fast forward to 2026 – 7 years after that initial interaction. I had the distinct pleasure of presenting our data for XMab819 to the ESMO – European Society for Medical Oncology audience at the 2026 ESMO Annual Meeting in Madrid. To offer some context for the data, this was an extremely heavily pretreated subset of patients – a prior VEGF-TKI and checkpoint inhibitor (CPI) were required, but notably, nearly 40% of patients had received 4 or more prior lines of therapy. In addition, over a third were ‘triply exposed’, having received a HIF2 inhibitor beyond a prior VEGF-TKI and CPI, and over 60% had received 2 or more prior VEGF-TKIs.
The results for XMab819 are bewildering
We reported a 45.5% response rate at the highest target dose. In addition, among triply pre-treated patients, response rate was 34.8% and in patients with 2 or more prior VEGF-TKIs it was 45.2%. As eloquently discussed at the meeting by Univ. Prof. Dr. Manuela Schmidinger, these are the highest rates of response with a novel agent for kidney cancer that we have seen in recent phase I trials that have reported – even besting certain combinations!
We are already moving assessment of XMab819 into earlier lines of therapy with a cohort that is open to patients who have progressed on nivolumab/ipilimumab. We are further assessing cohorts now of patients with elevated ENPP3 expression with papillary kidney cancer (a huge unmet need!), colon cancer and lung cancer.
I can’t wait to undertake subsequent studies that will get XMab819 into the treatment armamentarium – we need to do this quickly.
And for the junior investigators out there, it’s helpful to note that while this trial was a success, I have participated in many phase I trials that do not yield such promising results. The key is to believe in the science, believe in your collaborators and keep trying to push the field forward – our patients are depending us!”
You can also read:
25 Posts Not to Miss from ESMO Congress 2026: Day 5
