Highlighting Beneficial Adjuvant/Neoadjuvant Strategies for Kidney Cancer

The addition of immunotherapy before surgery and combinations with a pembrolizumab (Keytruda) backbone may enhance treatment for patients with kidney cancer in the adjuvant and neoadjuvant settings, according to David A. Braun, MD, PhD.

Braun, assistant professor at Yale School of Medicine and principal investigator in the Center of Molecular and Cellular Oncology within the Yale Cancer Center, discussed the current state of adjuvant and neoadjuvant therapies in treating patients with kidney cancer as well as research initiatives and clinical trials that may facilitate advancements in these settings. CancerNetwork® spoke with Braun following a presentation he gave at the 2025 Kidney Cancer Research Summit.

He began by contextualizing the current landscape of adjuvant therapy for this patient population. Braun explained that the introduction of pembrolizumab (Keytruda) in the adjuvant setting was a “game changer” but expressed that more could be done for this patient group.

To that end, Braun highlighted an emerging strategy where immunotherapy is administered before and after surgery, citing success in other diseases such as melanoma. Furthermore, Braun suggested that pembrolizumab could be added to combination therapies to bolster their efficacy, citing ongoing trials such as the phase 2 INTerpath-004 trial (NCT06307431) evaluating pembrolizumab with a vaccine-based approach and the phase 3 STRIKE trial (NCT06661720) evaluating the agent with tivozanib (Fotivda) as studies that will explore this area of interest.1,2

Transcript:

To give a bit of context, we had a prolonged period [spanning] tens of thousands of patients and decades of work in the adjuvant setting that was unfortunately unsuccessful, that didn’t help patients to live longer and significantly delay the recurrence of their cancer. The introduction of adjuvant pembrolizumab has been a game changer in that domain. [It was] the first to really show benefit.

But as I speak to my patients about it, it’s still far from a home run. Clearly, patients had benefit from it, but there are also many patients who do not. It’s hopefully an inflection point. It’s the idea that we can bend the curve, that we can decrease the chance of kidney cancer coming back, but it’s far from the end goal. We need to build on that, and I think there are multiple ways to do that.

One is this idea of not just doing immunotherapy after surgery in the adjuvant setting but before surgery as well, where there are maybe more targets or antigens present, where there are more functional immune cells. We have seen this take off in other diseases such as melanoma, [with] the idea of a substantial period of neoadjuvant therapy having quite substantial benefits, and I think that’s an area that needs to be investigated within kidney cancer.

The second is building on the success of pembrolizumab. What else can we add to it that might make it more efficacious? What might further augment immunity through something like a vaccine-based approach? And that’s the INTerpath-004 study that we’re helping to lead that builds on checkpoint inhibition and adds that steering wheel of a vaccine. Also other approaches like [the STRIKE trial], the Alliance trial led by Bradley A. McGregor, MD, which asks, “Can you eliminate angiogenic clones with the addition of tivozanib in a short-term but intensified period?” Those are the studies that are really going to build up. Of course, the addition of belzutifan [Welireg] is something that represents new mechanisms of action, and [I am] excited to see all those results in the coming years.

References

1. A study of adjuvant intismeran autogene (V940) and pembrolizumab in renal cell carcinoma (V940-004). (INTerpath-004). ClinicalTrials.gov. Updated May 13, 2025. Accessed July 21, 2025. https://tinyurl.com/2fdpnyhz
2. Testing the addition of the anti-cancer drug tivozanib to immunotherapy (pembrolizumab) after surgery to remove all known sites of kidney cancer (STRIKE). ClinicalTrials.gov. Updated June 26, 2025. Accessed July 21, 2025. https://tinyurl.com/ymx8zdhu