Neoantigen cancer vaccine shows encouraging activity in ccRCC

All 9 participants who received a neoantigen cancer vaccine for clear cell renal cell carcinoma (ccRCC) generated immune responses and remained free of disease recurrence at approximately 3 years following treatment, according to data from a phase 1 trial (NCT02950766) published in Nature.¹

All patients demonstrated an immune response.

“Patients with stage III or IV kidney cancer are at high risk of recurrence. The tools we have to lower that risk are not perfect and we are relentlessly looking for more,” explained co-senior author Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Cancer at Dana-Farber Cancer Institute in Boston, Massachusetts, in a news release on the findings.²

He added, “We’re very excited about these results, which show such a positive response in all 9 patients with kidney cancer.”

All 9 patients enrolled in the study had stage III or IV ccRCC and received multiple doses of the personalized cancer vaccine following surgery. Among all patients, 4 received the vaccine alone and 5 received the vaccine in combination with 2.5 mg doses of subcutaneous ipilimumab (Yervoy) at each vaccine site.

Within 3 weeks of vaccination, the investigators noted a substantial durable expansion of peripheral T cell clones, and 7 of 9 patients (77.8%) demonstrated T cell reactivity against autologous tumors.

Further, all patients demonstrated an immune response against the vaccine antigens, which included those targeting “RCC driver mutations in VHL, PBRM1, BAP1, KDM5C, and PIK3CA,” according to the authors.

“This strong and durable activation in T cells was encouraging and indicates that we're able to generate a long-lasting, anti-cancer immune response with the vaccine,” commented lead author David A. Braun, MD, an assistant professor of medicine, pathology, and urology at Yale School of Medicine in New Haven, Connecticut, in a news release.³

Data also showed that at a median follow-up of 40.2 months from surgery and 34.7 months from vaccination, no patients experienced a disease recurrence. The median disease-free survival (DFS) had not been reached at the time of data report.

Regarding safety, there were no dose-limiting (grade 3 or higher) toxicities reported. The most common adverse events included low grade injection site reaction (9 of 9 patients) and transient flu-like symptoms (8 of 9 patients).

The current study remains ongoing. A third cohort in the trial, which included patients who received the vaccine plus 5 mg of subcutaneous ipilimumab at each vaccine site, is still undergoing follow-up.

However, based on these initial findings, the authors wrote, “Our study therefore underscores the post-surgical adjuvant setting as an ideal context for [personalized cancer vaccines], as the minimal disease setting presents the possibility of effective consolidative and curative therapy.”

However, they suggest that further research in larger scale studies is warranted to confirm these findings.

Co-senior author Patrick A. Ott, MD, PhD, director of the center for cancer vaccines at Dana-Farber, added in the news release.² “These results support the feasibility of creating a highly immunogenic personalized neoantigen vaccine in a lower mutation burden tumor and are encouraging, though larger scale studies will be required to fully understand the clinical efficacy of this approach.”

Currently, a phase 2 study is ongoing to assess the efficacy a similar vaccine (V940; mRNA-4157) in combination with pembrolizumab in patients with RCC.⁴ The trial, titled INTerpath-004 (NCT06307431), is primarily comparing DFS with V940 plus pembrolizumab vs placebo plus pembrolizumab in the adjuvant setting. Primary completion of the trial is expected in January 2028.

References

1. Braun DA, Moranzoni G, Chea V, et al. A neoantigen vaccine generates antitumour immunity in renal cell carcinoma. Nature. 2025. doi:10.1038/s41586-024-08507-5

2. Cancer vaccine shows promise for patients with stage III and IV kidney cancer. News release. Dana-Farber Cancer Institute. Published online and accessed February 5, 2025. https://www.newswise.com/articles/cancer-vaccine-shows-promise-for-patients-with-stage-iii-and-iv-kidney-cancer

3. Personalized therapeutic vaccine ‘steers’ the immune system to fight kidney cancer. News release. Yale Cancer Center/Smilow Cancer Hospital. Published online and accessed February 5, 2025. https://www.newswise.com/articles/personalized-therapeutic-vaccine-steers-the-immune-system-to-fight-kidney-cancer

4. A study of adjuvant V940 and pembrolizumab in renal cell carcinoma (V940-004). (INTerpath-004). ClinicalTrials.gov. Last updated January 8, 2025. Accessed February 5, 2025. https://clinicaltrials.gov/study/NCT06307431