Design of a single-center, phase II trial to explore the efficacy and safety of ‘R-ISV-RO’ treatment in advanced tumors
Creators: name: Min, Limei
name: Wang, Xiaolu
name: Chen, Anni
name: Zhou, Yingling
name: Ge, Yuchen
name: Dai, Juanjuan
name: Chang, Xiaofeng
name: Sun, Wu
name: Liu, Qin
name: Zhou, Xia
name: Tian, Manman
name: Kong, Wentao
name: Zhu, Junmeng
name: Shen, Jie
name: Liu, Baorui
name: Li, Rutian
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Pharmacology
subject: Biotechnology
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences

description: <b>Background:</b> The authors' preclinical study has confirmed that RO adjuvant (composed of TLR 7 agonists [imiquimod/R837] and OX40 agonists) injected into local lesions induces the regression of both primary tumor and distant metastasis. The authors propose to realize local control and exert abscopal effect through an ‘R-ISV-RO’ <i>in</i> <i>situ</i> strategy plus anti-PD-1 monoclonal antibody in advanced tumors. <b>Methods:</b> This study is a single-center, exploratory, phase II trial to evaluate the efficacy and safety of R-ISV-RO plus anti-PD-1 monoclonal antibody in advanced tumors. 30 patients with one or more measurable extracerebral lesions that are accessible for radiation or injection will be enrolled. The primary endpoint is the objective response rate of target lesions. <b>Discussion/Conclusion:</b> The efficacy and safety of the novel strategy will be further validated through this clinical trial. <b>Clinical trial registration:</b> ChiCTR2100053870 (www.chictr.org.cn/) Radiotherapy and intratumoral injection of immunomodulatory drugs are the two main <i>in</i> <i>situ</i> vaccination techniques. Previous studies have shown that immune radiation induces immunogenic cell death to relieve the suppressive tumor immune microenvironment, while intratumoral injections directly stimulate tumor immune cells and raise local drug concentration to turn the tumor into a vaccine. Radiotherapy and intratumoral injection of immunomodulatory drugs are the two main <i>in</i> <i>situ</i> vaccination techniques. Previous studies have shown that immune radiation induces immunogenic cell death to relieve the suppressive tumor immune microenvironment, while intratumoral injections directly stimulate tumor immune cells and raise local drug concentration to turn the tumor into a vaccine. The authors designed a single-center, single-arm, open-label, exploratory, phase II clinical trial to evaluate efficacy and safety in patients with advanced solid tumors (intervention: ‘R-ISV-RO’ plus anti-PD-1 monoclonal antibody). The authors designed a single-center, single-arm, open-label, exploratory, phase II clinical trial to evaluate efficacy and safety in patients with advanced solid tumors (intervention: ‘R-ISV-RO’ plus anti-PD-1 monoclonal antibody). Mechanisms of tumors resistance: the tumor immunosuppressive environment found in immunogenic cold tumors presents significant challenges for tumor immunotherapy owing to low tumor-infiltrating lymphocyte infiltration and adoptive immune resistance.Application of Toll-like receptor (TLR) and OX40 agonist: in clinics, R837 (TLR 7 agonist) and OX40 agonist are frequently utilized. The authors' preclinical research has demonstrated the antitumor activity of the combination of TLR and OX40 agonists.Combination of immunotherapies: combining radiotherapy with intratumoral injection, while working in synergy with PD-1 monoclonal antibody, should reduce systemic therapeutic toxicity and generate a systemic antitumor immune response by making the targeted tumors more immunogenic. The above strategy could modify the condition of the tumor microenvironment, bring about the ‘cold-to-hot’ transition, remove drug resistance and boost the immune response to therapy. Mechanisms of tumors resistance: the tumor immunosuppressive environment found in immunogenic cold tumors presents significant challenges for tumor immunotherapy owing to low tumor-infiltrating lymphocyte infiltration and adoptive immune resistance. Application of Toll-like receptor (TLR) and OX40 agonist: in clinics, R837 (TLR 7 agonist) and OX40 agonist are frequently utilized. The authors' preclinical research has demonstrated the antitumor activity of the combination of TLR and OX40 agonists. Combination of immunotherapies: combining radiotherapy with intratumoral injection, while working in synergy with PD-1 monoclonal antibody, should reduce systemic therapeutic toxicity and generate a systemic antitumor immune response by making the targeted tumors more immunogenic. The above strategy could modify the condition of the tumor microenvironment, bring about the ‘cold-to-hot’ transition, remove drug resistance and boost the immune response to therapy. The safety and antitumor efficacy of immune checkpoint inhibitors in combination with <i>in</i> <i>situ</i> vaccines will be further validated. The safety and antitumor efficacy of immune checkpoint inhibitors in combination with <i>in</i> <i>situ</i> vaccines will be further validated.