An open-label single-center investigator-initiated exploratory clinical study in patients with refractory or recurrent solid tumors: ‘R-ISV-FOLactis’ trial

Abstract

Abstract Background: As a breakthrough tool for cancer immunotherapy, the therapeutic cancer vaccine, which includes personalized neoantigen vaccine and in situ vaccine, is in rapid development. In situ vaccination can be realized by radiotherapy and intratumoral immune injection. Additionally, immune checkpoint inhibitor is a common treatment modality for tumors. This study proposes to combine intratumoral injection, radiotherapy, and PD-1 inhibitors for patients with recurrent or metastatic solid tumors and subsequently evaluate the efficacyand safety. Methods/design: This exploratory clinical study is designed as an open-label, single-center trial aimed at treating patients with advanced solid tumors who are unresponsive or intolerable to standard treatment. Patients will be treated with hypofractionated radiotherapy, intratumoral injection of FOLactis, and PD-1 blockades. Additionally, 300mg cyclophosphamide will be added during intravenous administration of PD-1 blockades to inhibit regulatory T cells. Immune maintenance therapy with PD-1 blockades will be administered every three weeks until disease progression or the emergence of intolerable toxicity. The primary endpoint of this study is to observe the objective efficacy and safety of the combined regimen, with the secondary endpoint to evaluate abscopal effects and the correlation between the immunological rationale and efficacy. Discussion: Both radiotherapy and intratumoral immune injection are approaches to conducting in situ vaccination. Their combination can enhance anti-tumor immunity by targeting multiple links of the cancer-immunity cycle. PD-1 blockade, a kind of immune checkpoint inhibitor, has garnered significant attention in tumor immunotherapy research in recent years. In this study, a triple combination of radiotherapy, intratumoral immune injection, and intravenous PD-1 inhibitor will be utilized to treat patients with advanced solid tumors to trigger antitumor immunity. The combined treatment is expected to be feasible and effective and provide a novel option for the comprehensive treatment of cancer. Trial registration: ChiCTR. gov.cn: ChiCTR2200060660.