Sufferers with kidney most cancers might profit from scientific trial enrollment, as Dr. Michael Serzan defined whereas discussing early outcomes from the STELLAR-002 research.
Dr. Michael Serzan sat down for an interview with CURE to debate the significance of scientific trial enrollment for sufferers with renal cell carcinoma, a sort of kidney most cancers, in addition to mentioned latest findings from the STELLA-002 research which have been just lately introduced on the 2025 ASCO Annual Assembly.
“In case you are eligible for a scientific trial, it is essential to debate the potential advantages of enrolling… We’re agency believers that it is the solely means we advance the science of the sector. Many occasions, sufferers obtain even higher care whereas on scientific trials as a result of we’re actively making an attempt to maneuver the sector ahead and utilizing tomorrow’s therapies at present,” Serzan emphasised within the interview.
Serzan serves as a medical oncologist within the Lank Heart for Genitourinary Oncology at Dana-Farber Most cancers Institute and is an teacher of drugs at Harvard Medical Faculty, situated in Boston.
CURE: To kick issues off, what updates have been shared from the part 1b STELLAR-002 research on the 2025 ASCO Assembly?
Serzan: First, thanks a lot for having me and for internet hosting this crucial session to higher inform sufferers and their caregivers about updates from ASCO 2025. My title is Dr. Michael Serzan, and I’m a medical oncologist on the Dana-Farber Most cancers Institute. I am joyful to stroll by the STELLAR-002 research.
For some context, this research was performed for sufferers with metastatic kidney most cancers, that means most cancers that had unfold to distant components of the physique. We’re very lucky to have many therapy choices that haven’t solely helped sufferers reside higher, but in addition reside longer. This explicit research aimed to analyze a brand new mixture of therapies designed not solely to shrink most cancers, however hopefully to attain long-term management. It appeared on the security, tolerability, effectiveness of the medication, and the way lengthy sufferers remained on the research.
The STELLAR-002 research was a part 1 trial that utilized the brand new VEGF TKI (Vascular Endothelial Progress Issue Tyrosine Kinase Inhibitor), zanzalintinib (XL092). This medicine primarily targets the blood provide of clear cell kidney most cancers and is similar to a drug referred to as Cabometyx (cabozantinib), which is certainly one of our foundational therapies for kidney most cancers sufferers. The important thing distinction is that zanzalintinib has a a lot shorter half-life. This implies if sufferers expertise negative effects and have to discontinue remedy, we are able to cease the drug, and people negative effects might resolve extra rapidly.
The STELLAR program mixed zanzalintinib with Opdivo (nivolumab), which is certainly one of our customary immunotherapies. The second arm of the research checked out zanzalintinib plus Opdivo and Opdualag (relatlimab-rmbw), a brand new immunotherapy drug that targets the LAG-3 receptor on the floor of immune cells. The research was actually making an attempt to find out if there have been variations in how nicely the medication have been tolerated and the way efficient they have been at treating the most cancers when evaluating the zanzalintinib/Opdivo arm versus the zanzalintinib/Opdivo/Opdualag arm.
For sufferers who’re newly recognized with clear cell renal cell carcinoma, how does this mix remedy of zanzalintinib and Opdivo with or with out Opdualag evaluate to current frontline therapy choices?
It is a terrific query, and one which we regularly focus on at our massive annual conferences. I’ll put a caveat in that this was a small, comparatively small research. It was a part 1 trial with solely 80 sufferers, 40 in every arm — designed primarily to see how nicely this mix was tolerated. After we attempt to evaluate it with at the moment out there choices, it’s essential to recollect these are totally different research with totally different affected person populations and medicines, so it’s not an ideal comparability. Nonetheless, we are inclined to make these comparisons anyway.
What I might say in regards to the outcomes from STELLAR-002 is that the negative effects within the doublet — zanzalintinib plus Opdivo — versus the triplet — zanzalintinib plus Opdivo and Opdualag — have been pretty related. A few third of sufferers skilled negative effects, which have been [consistent] with what we sometimes see with all these therapies. The most typical ones have been hypertension, diarrhea, liver and thyroid abnormalities, and pores and skin rash. If sufferers skilled these negative effects, we managed them by lowering doses or quickly holding the medicines.
One notable a part of the presentation was that only a few sufferers in both arm ended up stopping therapy altogether. Investigators appeared capable of establish what should be blamed for the negative effects, maintain the medicine, after which resume therapy.
As for tumor responses: within the doublet arm, we noticed a response fee of simply over 60% and a illness management fee of about 90%. Which means about 60% of sufferers had their tumors shrink, and about 90% had their tumors shrink or keep steady.
After we take a look at the triplet arm, we noticed considerably decrease charges — a response fee round 40%, although the illness management fee was nonetheless about 90%. Once more, small numbers right here with 40 sufferers in every arm, however it’s intriguing; you’d suppose that the triplet would present the next response fee versus the doublet, however we didn’t see that but on this research.
We additionally checked out progression-free survival, which was really a bit longer within the doublet arm at about 18 months versus about 13 months for the triplet. It’s intriguing to see.
The first finish level was security and tolerability, and these mixtures appeared pretty related in that regard. That mentioned, it was a bit of [disappointing] that the triplet didn’t appear to supply higher or longer responses. Nonetheless, this can be a mixture value exploring, particularly as we proceed trying to find new medication and regimens for sufferers with kidney most cancers.
On condition that this was an early-phase research, what are the following steps earlier than this mix might develop into extra extensively out there or advisable as a regular of care?
The bar for kidney most cancers is sort of excessive. As I discussed at the start, we’re lucky to have many mixture therapies that work reasonably nicely, making it difficult to unseat or outperform these present requirements of care. For sufferers with clear cell kidney most cancers, which was the research inhabitants in STELLAR-002, we would wish to see a part 2 research demonstrating a bit extra of the efficacy of this mix. Finally, it will must be in contrast in opposition to a few of our customary therapies earlier than it might develop into out there for sufferers.
I’ll say there’s a scientific trial out there for sufferers with non-clear cell kidney most cancers that’s evaluating zanzalitinib plus Opdivo to Sutent (sunitinib). That is the STELLAR-304 research, a big trial that’s actually making an attempt to determine the position of zanzalitinib plus Opdivo in that non-clear cell inhabitants. We actually look ahead to seeing the outcomes of that research and its potential to vary take care of sufferers with non-clear cell kidney most cancers.
What ought to sufferers ask their care groups in the event that they’re excited about collaborating in a scientific trial like STELLAR-002 or accessing related therapies sooner or later?
That is a terrific query. I at all times inform sufferers, each time they obtain a brand new most cancers prognosis, to ask their care group — whether or not it is their oncologist, urologist, or radiation oncologist — “Do you suppose I might be eligible for a scientific trial?” If they’re, then they need to perceive what that scientific trial entails.
I wish to tackle a standard fantasy that many sufferers consider: that scientific trials are solely for many who have exhausted all different therapy choices. That could not be farther from the reality. As we noticed within the STELLAR-002 research, this can be a brand-new mixture with organic rationale that we hope will enhance the usual of care. All medication ever accredited for most cancers sufferers have gone by this kind of research. So, I wish to dispel the notion that scientific trials are just for sufferers who’ve exhausted all strains of remedy. I firmly consider they play an important position for sufferers throughout all the illness spectrum.
In case you are eligible for a scientific trial, it is essential to debate the potential advantages of enrolling, the potential dangers or downsides, and a number of the logistics concerned. In case your establishment would not provide a scientific trial, I feel it is crucial to ask for a second opinion at an establishment that does, as a result of we’re agency believers that it is the solely means we advance the science of the sector. Many occasions, sufferers obtain even higher care whereas on scientific trials as a result of we’re actively making an attempt to maneuver the sector ahead and utilizing tomorrow’s therapies at present.
Transcript has been edited for readability and conciseness.
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