David Braun, MD, on phase 2 trial of an individualized neoantigen therapy for RCC

In this video, David A. Braun, MD, PhD, describes background and design of the phase 2 INTerpath-004 trial (NCT06307431), which is assessing the safety and efficacy of a neoantigen targeting personalized cancer vaccine, V940, in patients with renal cell carcinoma. The study design was presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California. Braun is an assistant professor at Yale Cancer Center in New Haven, Connecticut.

Video Transcript:

Could you describe the background/rationale for this trial?

The rationale for this is [that] we know that immune checkpoint inhibitors have been transformative for the management of advanced kidney cancer and high-risk resectable kidney cancer, but there's still many patients that don't benefit. Very naively, I think of those immune checkpoint inhibitors as lifting the brakes on the immune system, but not necessarily telling the immune system where to go or what to attack. The idea behind a personalized cancer vaccine, particularly one that targets neoantigens, is, can we add a steering wheel? Can we tell the immune system exactly where to go to attack the cancer in a very specific way? That's really the rationale and motivation for the study.

For the phase 1, which we just published, it was a question of feasibility, safety, and mechanism. Were we able to create a personalized cancer vaccine? That's not necessarily a trivial thing in kidney cancer. Was it safe? The answer to both of those, fortunately, were yes for all of the 9 patients who were enrolled. The next question is, is it doing what we think it should do, which is steering the immune system towards targeting neoantigens? Absolutely it did. It did that for all 9 patients, and it did so in a durable way, meaning those responses lasted months or even years after vaccination had completed. I think reassuringly and promisingly, none of those 9 patients, despite being at a high-risk, had their kidney cancer recur or come back. But it's still a very small study, so we have to be cautious about the clinical activity. That's the setup for the INTerpath-004 study, taking off where this one left off, which is to evaluate the efficacy at a much larger scale.

How is the trial designed? What are the key end points?

This is an adjuvant trial for high-risk resected kidney cancer. It's in many ways, fairly similar eligibility criteria to the KEYNOTE-564 trial, which is the trial that led to the approval of adjuvant pembrolizumab for kidney cancer. There are some small tweaks. Most notably that it includes some patients with papillary renal cell carcinoma, not just clear cell and that intermediate high category, for the pT3s, it does require a higher grade. So, before it was pT3, any grade; now it's pT3, grade 3 or 4. But the remainder of the criteria is the stuff we're used to from the KEYNOTE-564, criteria, the same ones we use in our clinic day-to-day to help inform discussions about adjuvant therapy for patients.

With that eligibility, patients are randomized. Everyone gets the standard of care. So, everyone gets pembrolizumab, but then it's randomized 50/50 to either pembrolizumab plus placebo or pembrolizumab plus the V940 neoantigen targeting personalized cancer vaccine. The primary end point is disease-free survival; that’s a standard for an adjuvant trial. It's about 270 patients, so about 130-135 in each arm. It's not only randomized, but blinded, both to the patients and also to the investigators. I think this is the next step for testing the clinical activity of this agent.

This transcript was AI generated and edited by human editors for clarity.