Phase 1b trial of PolyPEPI1018 cancer vaccine plus TAS-102 for advanced, chemo-refractory, microsatellite-stable metastatic colorectal cancer

Immunotherapy has demonstrated limited efficacy in the treatment of microsatellite-stabel metastatic colorectal cancer (MSS mCRC). A phase 1b study at the Mayo Clinic (Rochester, MN) evaluated the combination of the off-the-shelf multipeptide vaccine PolyPEPI1018 and TAS-102 chemotherapy for MSS mCRC. The study enrolled 15 patients who had received ≤ 2 previous lines of therapy (80% with liver metastases; 67% with KRAS mutations). Patients were treated for seven 4-week cycles or until disease progression. Adverse events related to the vaccine were grade 1 and 2 local skin reactions. Grade 3 AEs (n=15) at least possibly related to treatment were fatigue, decreased lymphocyte and neutrophil counts, and diarrhea. There were no objective tumor responses; the disease control rate was 53.3%. The median progression-free survival and overall survival were 4.0 months and 8.7 months, respectively. In post hoc subgroup analyses, patients without active liver metastases had improved mPFS of 9.7 months and mOS of 14.8 months. In addition, patients who were expected to have broader immune responses to vaccine based on HLA genotype had longer mOS (10.3 versus 4.6 months). The authors conclude that addition of PolyPEPI1018 to TAS-102 was safe and induced immunological responses that were associated with improved clinical outcomes. Further investigation of this combination is warranted.