Phase 3 Results Point to a Path Forward for Cancer Vaccines

In an interview with Targeted Oncology, Karen E. Knudsen, PhD, CEO of the Parker Institute for Cancer Immunotherapy, discussed results from the phase 3 INTerpath-001 trial (NCT05933577), presented at the 2026 ESMO Congress, and what they mean for the future of cancer therapeutic vaccines.

In INTerpath-001, adding the individualized mRNA neoantigen therapy intismeran autogene to pembrolizumab (Keytruda) reduced the risk of recurrence or death by 42% vs pembrolizumab alone in patients with resected stage IIB to IV melanoma (hazard ratio [HR], 0.58; 95% CI, 0.45–0.75; P < .001). The combination also reduced the risk of distant metastasis or death by 38% (HR, 0.62; 95% CI, 0.45–0.85; P = .002).

Knudsen described the study as one of several well-conducted trials showing a path forward for therapeutic cancer vaccines. She noted that the ESMO presentation allowed a closer look at the data than the topline results released earlier in the summer. In addition to the reductions in recurrence and metastasis, she highlighted the regimen’s tolerability, explaining that patients gained the benefit of the vaccine with little added toxicity. She also observed that the benefit across prespecified subgroups appeared broader than the initial announcement suggested.

The timing of the effect stood out as well. In a prespecified sensitivity analysis, recurrence-free survival did not differ between arms during the first 6 months (HR, 0.99) but separated thereafter (HR, 0.42). According to Knudsen, this delay is consistent with the time a therapeutic vaccine would need to take hold and durably train the immune system, and it offers a hint about the therapy’s mechanism of action.

Knudsen emphasized that delaying or preventing recurrence and metastasis is highly meaningful for patients with melanoma. However, she cautioned that overall survival data, which were immature at this first interim analysis, will be essential to understanding the full impact of the regimen.