Advanced Unresectable Hepatocellular Carcinoma

This clinical study aims to evaluate the efficacy and safety of Retlirafusp alfa Injection (SHR-1701) combined with apatinib in patients with advanced hepatocellular carcinoma (HCC) who have experienced disease progression after first-line targeted combined immunotherapy, and provide clinical evidence for the second-line treatment of advanced HCC. A total of 80 patients with radiologically or pathologically confirmed advanced/unresectable hepatocellular carcinoma with disease progression after prior first-line targeted-immunotherapy will be enrolled within 2.5 years. All enrolled patients will receive intravenous infusion of SHR-1701 at 30 mg/kg every 3 weeks in combination with oral apatinib 250 mg once daily; treatment will be maintained until disease progression or intolerable adverse toxicity occurs. The primary study endpoint is objective response rate (ORR).

This study was a multicenter, open-label phase I clinical trial. This trial will include 36 patients with advanced unresectable hepatocellular carcinoma. Blood samples were obtained during the course of treatment to measure the relative parameter. All Investigational Medicinal Products (IMP) were discontinued after the total cycle.

RBS2418 is a targeted immune modulator that inhibits ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). It is designed to promote anti-tumor immunity by preserving endogenous 2'-3' cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from hydrolysis, thereby activating antigen-presenting cells and promoting robust T cell activation. Ideally, RBS2418 acts synergistically with CTLA-4 inhibitors, such as those in the STRIDE regimen (Tremelimumab plus Durvalumab). The hypothesis is that RBS2418 combined with STRIDE will be safe, well-tolerated, highly immunogenic, and enhance anti-tumor responses in adult participants with advanced, unresectable hepatocellular carcinoma (HCC) compared to STRIDE alone.