Abstract 442P
Background
Colorectal cancer (CRC) is among the highest incidence and mortality cancer rates. Immune check-point blockade (ICB) showed clinical benefit in patients (pts) in MSI metastatic CRC (mCRC) but not in MSS pts. Cancer vaccines with autologous dendritic cells (ADC) could be a complementary therapeutic approach to ICB with potentially synergistic effects.
Methods
This was a phase I/II multicentric open labeled, with translational sub-studies, to evaluate the safety, pharmacodynamics and anti-tumor effects of avelumab (anti-PDL1) + ADC vaccine in heavily pre-treated MSS mCRC pts. Treatment consisted of avelumab 10 mg/kg every 2 weeks + id ADC vaccine at days 1, 14, 28, 42 and 56, and thereafter every 6 months until disease progression (max 6 additional doses) or unacceptable toxicity. Samples were collected at day 0 and 56 to evaluate pharmacodynamics changes: cytokines, chemokines, immune phenotype of PBMCs and RNA-seq immune-metabolic signature (IMS). Primary objective was to determine the MTD and the efficacy of the combination. Primary end-point was 40% PFS at 6 months with a 2 Simon Stage.
Results
19 pts were treated. Combined therapy was safe and well tolerated. An interim analysis (Simon design first-stage) recommended early termination because 2/19 (11%) were disease free at 6 months. 4 pts (21,05%) experienced stable disease, 10 pts (52,63%) had progressive disease and 4 pts (21.05%) experienced hyper progressive disease (HPD) 1 pt was not evaluable. Median PFS was 3.1 months [2,1 – 5,3] and OS was 12,2 months [3,2 – 23,2]. Stimulation of immune response was observed with changes of cytokine levels after treatment (VEGFC, SDF1a, MMP9, MCP1), although no significant differences were observed on PBMCs subpopulations. The evaluation of RNA-seq IMS did not correlated with clinical outcomes. HPD was observed in different immune-metabolic micro-environments (IMME).
Conclusions
The combination of avelumab and ADC vaccine is safe and well tolerated, increased the immune response but exhibited modest clinical activity. We did not find correlations between IMME and clinical efficacy, which emphasize the complexity of the immune-system.
Clinical trial identification
NCT03152565.
Editorial acknowledgement
Legal entity responsible for the study
GEMCAD (Grupo Español Multidisciplinar en Cancer Digestivo).
Funding
Merck.
Disclosure
All authors have declared no conflicts of interest.