Guan-Tarn Huang

Purpose: 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 and Methods: 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. Results: 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. Conclusion: 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.

Supplementary Figure 3: Forest Plot of Hazard Ratio of Treatment Effect on Progression-Free Survival, According to Baseline Prognostic Factors. (A) Intent-to-treat population, n=701; (B) Subset: Solitary lesion (BCLC A) and RFA dwell time {greater than or equal to}45 min, n=285.

Supplementary Tables 1-8 and Supplementary Figures 1-3 legends Supplementary Table 1: List of Investigators for the HEAT Study Supplementary Table 2: Summary of RFA Treatment Supplementary Table 3: Stepwise Multivariate Cox Modelling Results Supplementary Table 4: Overall Survival According to Stage Supplementary Table 5: Evaluation of Treatment Failure Supplementary Table 6: Overview of Treatment-Emergent Adverse Events Supplementary Table 7: Treatment-Emergent Adverse Events by Preferred Term Supplementary Table 8: Key Treatment-Emergent Adverse Events Among Subjects With a Solitary Tumor by 45-Minute RFA Cutpoint

Supplementary Figure 1: Computational Modeling Study.

Supplementary Figure 1: Computational Modeling Study.