Adjuvant TTFields + Pembrolizumab + Temozolomide Lifts mPFS to 12 mo in Newly Diagnosed GBM

TTFields therapy activates type-I-interferon signalling. This single-arm phase 2 study (NCT03405792) evaluated whether adding a PD-1 blockade to the EF-14 backbone could matter. Twenty-six patients, post-chemoradiation, received adjuvant TTFields (≥18 h/day) in combination with temozolomide and pembrolizumab. The mPFS was 12.0 mo compared to 5.8 mo in matched TTFields-TMZ controls (HR 0.38, p = 0.0026). The mOS reached 24.8 mo vs 14.6 mo (HR 0.52, p = 0.048). Only 7.5% of treatment-related toxicities were grade ≥3, and serious immune AEs were rare. For context, the pivotal EF-14 trial of TTFields+TMZ alone achieved a mPFS of 6.7 mo and a mOS of 20.9 mo under similar patient selection; thus, this triplet therapy appears to extend OS by approximately 5 months without any new safety signals.