Study of Isatuximab and Cemiplimab in Relapsed or Refractory Natural Killer/T-cell Lymphoid Malignancy

Conditions

• Natural Killer/T-cell Lymphoma
• Refractory Natural Killer/T-cell Lymphoma
• Relapsed Natural Killer/T-cell Lymphoma

Eligibility Criteria

Sex

ALL

Age

19 Years - 85 Years

Healthy Volunteers

Not accepted

Interventions

• Isatuximab — DRUG
  The treatment cycle will be repeated up to 2 years. If a patient shows disease progression or unacceptable toxicity, the study treatment will be discontinued and followed up for efficacy and safety after the discontinuation of study treatment.
• Cemiplimab — DRUG
  The treatment cycle will be repeated up to 2 years. If a patient shows disease progression or unacceptable toxicity, the study treatment will be discontinued and followed up for efficacy and safety after the discontinuation of study treatment.

Study Details

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.

Key Dates

Start date

Jun 25, 2021

Status verified

Apr 2026

Primary completion

Apr 30, 2023

Completion

Apr 1, 2026

Study Design

Enrollment

37 participants (actual)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Isatuximab and Cemiplimab combined therapy
  Drug : Isatuximab 1 cycle : 10mg/kg IV every week. It is administered on Day 2, Day 9, Day 16, Day 23. 2\~6 cycle : 10mg/kg every 2 weeks . It is administered on Day 2, Day 16. 7th cycle and beyond : 10mg/kg IV every 3 weeks. It is administered on Day 2. Drug : Cemiplimab 1st - 6th cycle : 250mg IV every 2 weeks. It is administered on Day 1, Day 15. 7th cycle and beyond : 350mg every 3 weeks. It is administered on Day 1.

Primary Outcome Measure

Complete response rate [ Time Frame: 3 years after completion of the clinical trial drug administration of the last subject ]