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Azacitidine

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5-azacytidine + 1x10\^8 NKR-2 CAR-T Cells

5-azacytidine + 3x10\^8 NKR-2 CAR-T Cells

5-azacytidine + 1x10\^9 NKR-2 CAR-T Cells

The treatment consists in six consecutive cycles of AZA, administered at days

1 to 7 of a 28-day cycle. Patients will be treated with 8 injections of NKR-2 at day 9 and 23 of AZA cycles 2-3-4 and 5.

NKR-2 CAR-T Cells

Frederic Lehmann, MD

This open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive chemotherapy or hematopoietic stem cell transplantation.

This Phase I study is divided into three sequential cohorts evaluating three different dose-levels of NKR-2 (1x108, 3x108 and 1x109 NKR-2 per injection) using a 3+3 design evaluate. Further patients will be enrolled at the RecD to reach 9 evaluable patients in total at the RecD.

The study consists of a screening phase, a treatment administration phase and a follow-up phase divided into treatment follow-up (TFU) and long-term safety follow-up (LTSFU). For each patient who received at least one NKR-2 administration, the overall study duration will be 15 years after first NKR-2 administration.

This open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive induction chemotherapy. The treatment consists in six consecutive cycles of AZA, administered at days

1. to 7 of a 28-day cycle. Patients will be treated with 8 injections of NKR-2 at day 9 and 23 of AZA cycles 2-3-4 and 5.

   This Phase I study is divided into three sequential cohorts evaluating three different dose-levels of NKR-2 (1x108, 3x108 and 1x109 NKR-2 per injection) using a 3+3 design. Further patients will be enrolled at the RecD to reach 9 evaluable patients in total at the RecD. The study consists of a screening phase, a treatment administration phase and a follow-up phase divided into treatment follow-up (TFU) and long-term safety follow-up (LTSFU). For each patient who received at least one NKR-
2. administration, the overall study duration will be 15 years after first NKR-

2 administration. Patients will be asked to complete a total of 54 visits during the treatment administration phase, and 5 visits during the treatment follow-up phase. During the LTSFU, yearly visits will be scheduled (up to Visit Y15).

This open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive chemotherapy or hematopoietic stem cell transplantation.

This Phase I study is divided into three sequential cohorts evaluating three different dose-levels of NKR-2 (1x108, 3x108 and 1x109 NKR-2 per injection) using a 3+3 design evaluate. Further patients will be enrolled at the RecD to reach 9 evaluable patients in total at the RecD.

EPITHINK: Epigenetic Drug Treatment and Therapeutic Immunotherapy With NKR-2

An Open-label, Phase I Study to Assess the Safety of NKR-2 Treatment Administered Concurrently With 5-azacytidine in Treatment-naïve Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients Not Candidates for Intensive Therapy

The occurrence of DLTs during the study treatment phase (up to month 6)

The occurrence of AEs and SAES and any toxicity linked to study participation until the end of the administration phase, and until the end of the treatment follow up (Month 24).

The overall survival (OS), will be evaluated for all patients that received treatment from apheresis until the 24 month study visit.

The Relapse Free Survival (RFS),patients that do not have an event of Progressive disease, will be evaluated for all patients that received treatment from apheresis until the 24 month study visit.

The Event Free Survival (EFS), will be evaluated for all patients that received treatment from apheresis until the 24 month study visit.

The objective clinical response rate (ORR) post the first NKR-2 administration will be evaluated via bone marrow biopsy and aspirate analysis for disease status.

The duration of response, for patients that achieve complete response or partial response post the first NKR-2 administration will be evaluated for all patients that receive at least the first dose of NKR-2 infusion.

The objective clinical response rate (ORR) post retreatment with NKR-2 administration will be evaluated via bone marrow biopsy and aspirate analysis for disease status.

The duration of response, for patients that achieve complete response or partial response post the first NKR-2 administration.

The cumulative incidence of relapse (CIR), will be evaluated for all patients that are treated with at least one administration of NKR-2

The cumulative incidence of Death (CID), will be evaluated for all patients that are treated with at least one administration of NKR-2

The non-relapse mortality rate (NMR), will be evaluated for all patients that are treated with at least one administration of NKR-2

For AML patients: the incidence of CR, CRMRD-, CRi, MLFS, PR, or SD post NKR-2 administrations until the end of the treatment follow-up (till 24 months after first NKR-2 treatment administration),

For MDS patients: the incidence of CR, PR, marrow CR, cytogenic response, hematologic improvement or SD post NKR-2 administrations until the end of the treatment follow-up (till 24 months after first NKR-2 treatment administration)

The number of patients deemed eligible for an allogeneic stem cell transplantation at screening based on aged and comorbidities by the Investigator who are able to achieve this outcome with investigational treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
EPITHINK: Epigenetic Drug Treatment and Therapeutic Immunotherapy With NKR-2	NCT03612739	AML, Adult Myelodysplastic...	NKR-2 CAR-T Cel...	18 Years -	Celyad Oncology SA
EPITHINK: Epigenetic Drug Treatment and Therapeutic Immunotherapy With NKR-2	NCT03612739	AML, Adult Myelodysplastic...	NKR-2 CAR-T Cel...	18 Years -	Celyad Oncology SA

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