Natural Killer/T-cell Lymphoma Clinical Trial
Official title:
A Phase II Study of Isatuximab and Cemiplimab in Relapsed or Refractory Natural Killer/T-cell Lymphoid Malignancy : Nick Name - ICING Study
This study is to analyze the efficacy of PD1 inhibitor and anti-CD38 antibody in relapsed or refractory NK/T-cell lymphoid malignancy. The investigational products of this study are cemiplimab (PD1 inhibitor) and isatuximab (anti-CD38 antibody). The rationale for the use of cemiplimab in patients with NK/T-cell lymphoid malignancy is the aforementioned PD-L1 expression in tumor cells of ENKTL and ANKL. In addition, the proven efficacy of pembrolizumab in relapsed or refractory ENKTL support the use of PD1 inhibitor as a salvage therapy for this disorder. The addition of isatuximab to cemiplimab might induce synergistic activity because CD38-mediated immunosuppression as a mechanism of tumor cell escape from PD-1/PD-L1 blockade. Furthermore, targeting CD38 by isatuximab can preferentially block immunosuppressive regulatory T-cells and thereby restore immune effector function against multiple myeloma. These functions of CD38 blocking antibody might help to improve the efficacy of immune checkpoint inhibitor such as PD1 inhibitor. Given the presence of antibody-mediated cytotoxicity and direct anti-tumor effect of isatuximab against CD38-positive tumor cells, the combination of isatuximab with cemiplimab might show the synergistic activity resulting more improved treatment outcome than PD1 inhibitor alone. Thus, The investigators designed a phase II study of cemiplimab and isatuximab for patients with relapsed or refractory ENKTL and ANKL. In this study, The investigators analyze the efficacy of this novel combination and their adverse effects.
This clinical trial is a study that uses two antibodies called 'Isatuximab' and 'Cemiplemab' as a rescue anticancer therapy for patients with relapsed or refractory'NK/T cell lymphoma'. Cemiplimab is an antibody against the PD1 protein of cytotoxic T cells. By inhibiting the binding of the PDL1 protein expressed on the surface of tumor cells, cancer cells use the PDL1 protein expressed on the surface of their cells to the tumor immune function It works to prevent getting involved. When the interaction between PD1 and PDL1 protein is suppressed in this way, T cells in human's body attack and kill cancer cells, and cancer cells are killed through this process. To date, immuno-cancer drugs that inhibit the interaction of PD1 and PDL1 proteins have already been developed other than Cemiplimab, and have proven excellent therapeutic effects in lung cancer and Hodgkin's lymphoma. Therefore, the investigators have started this clinical trial because Cemiplimab, one of the immuno-cancer drugs, is expected to be effective in the 'NK/T cell lymphoma' that you have been diagnosed with. However, the effect of Cemiplimab in the disease has not yet been proven, and a research report has recently been published that other anticancer drugs that inhibit the PD1 protein may be effective in'extralymphatic NK/T cell lymphoma'. However, this is not conclusive because it is a study involving a small number of patients. However, if this clinical trial proves that cemiplimab is effective in 'NK/T cell lymphoma', it could contribute to the development of new treatments for this disease. In addition, all of the previous studies have studied the therapeutic effect using only a single antibody that inhibits the PD1 protein, but in this study, an antibody against the CD38 antigen called isatuximab is used together. The CD38 antigen is expressed in several hematocrit cells, and in multiple myeloma, antibodies to CD38 are already used as standard treatments for relapsed or refractory diseases. However, the high frequency of expression of CD38 antigen on the surface of tumor cells of NK/T cell lymphoma is expected as a therapeutic target, but its therapeutic effect has not yet been proven. Istuximab used in this study is an antibody targeting CD38, and can be expected to kill tumor cells expressing CD38, so when administered in combination with cemiplimab, its therapeutic effect can be increased. In this study, patients diagnosed and treated as'NK/T cell lymphoma' but did not reach cure and the disease worsened, or patients who experienced a cure but later recurred. The investigators want to evaluate the effectiveness. Through this, the goal is to improve the prognosis by discovering a new treatment that is ultimately effective for the treatment of relapsed or refractory 'NK/T cell lymphoma.' ;