In Situ Vaccination with Poly-ICLC Combined with Systemic Nivolumab for the Treatment of Unresectable Hepatocellular...

Unresectable hepatocellular carcinoma (HCC) presents significant therapeutic challenges. While immune checkpoint inhibitors (ICIs) are part of the current standard of care, combining poly-ICLC as an in situ vaccination with an ICI may enhance treatment efficacy. The study investigated the safety and therapeutic effects of combining poly-ICLC with nivolumab, an ICI, in patients with unresectable HCC.

Patients with unresectable HCC were enrolled to receive intratumoral and intramuscular poly-ICLC injections along in combination with nivolumab infusions. The primary endpoint was safety, and secondary endpoints included objective response as measured by mRECIST and changes in serum alpha-fetoprotein (AFP) levels. Gene expression profiling, pathway analysis, and immune cell type deconvolution were conducted using NanoString GeoMx Digital Spatial Profiling.

Four patients were enrolled. The combination therapy was safe and well-tolerated. Among them, one patient achieved a complete response (CR), and another achieved a partial response (PR). Both responders showed significant declines in serum AFP levels. Notably, the patient with CR showed eradication of cancerous component of the portal vein thrombus, and an abscopal effect was observed in the patient with PR. Gene analysis indicated that interferon-gamma signaling was the most enriched pathway in tumors of the responders.

This combination therapy was safe and effective, with two out of four patients demonstrating objective responses. These preliminary findings warrant further investigation into larger clinical cohorts.