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.
• Patients should be histologically diagnosed with extranodal NK/T-cell lymphoma or aggressive NK-cell leukemia.
• Patient should be previously treated with at least one type of chemotherapy regimen including autologous stem cell transplantation.
• Patient should have relapsed or refractory disease before enrollment.
• Patient written informed consent obtained prior to any screening procedures.
• Patient should be a male or female ≥ 19 years (Maximum 85 years)
• Patient should have at least one measurable lesion on the CT or PET/CT scan. In case of PET/CT, diagnostic quality CT part of PET/CT is needed to define measurability. Cf. If a patient only has non-measurable lesion on the CT or PET/CT scan (e.g. bone marrow involvement, malignant effusion, and hemophagocytic lymphohistiocytosis), its association with disease progression or relapse should be determined by an investigator. Based on investigators' decision, patients with non-measurable lesion could be enrolled.
• Patient should have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 which is not declining during the last 2 weeks before the signature of the main study Informed Consent Form (S-ICF).
• Patient should have adequate bone marrow function as defined by the following laboratory values: Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L; Platelets ≥ 50 x 109/L; Hemoglobin ≥ 8.0 g/dL Cf. If the cause of cytopenia is related with bone marrow involvement of tumor cells, a patient could be enrolled after blood transfusion or G-CSF support by investigator's decision.
• Female patient should fulfill the following criteria 1) Pregnancy test: Negative serum or urine pregnancy test at screening for women of childbearing potential; 2) Contraception: Highly effective contraception for both male and female subjects throughout the study and for at least 6 months after last administration of study drug if the risk of conception exists.
⁃ Patient should have adequate organ function as defined by the following laboratory values: Serum Creatinine ≤ 2.0 × ULN; Serum Bilirubin ≤ 2.0 × ULN; AST and ALT ≤ 3 × ULN. Cf. If the values of liver function tests more than the above-mentioned criteria are related with disease relapse or progression to liver, a patient could be enrolled by investigator's decision in case of ≤ 5.0 × ULN.
⁃ Patients should have archived tumor tissue or fresh tissue sample obtained from re-biopsy at relapse available for targeted sequencing.
⁃ In case of written consent to participation in clinical study: Must sign the subject consent form that states the blood sampling done according to the study protocol and that the subject has comprehended the purpose and the necessary procedures of clinical study with intention to participate in the clinical study (or signed by the subject's representative).