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NKR-2

Phase 1

AML | Monoclonal antibody | Other |IQVIA Holdings, Inc.|Last Updated: May 4, 2021

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
CONTROLLEDBiomarker
Total Trials1
Total Enrollment21
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03466320DEPLETHINK - LymphoDEPLEtion and THerapeutic Immunotherapy With NKR-2PHASE1 COMPLETED 21Sep 18, 2018Feb 1, 2021May 4, 20217 United States, Belgium
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Study Endpoints
Primary Endpoints
The occurrence of Dose-limiting toxicities (DLT) during the study treatment until 3 weeks after first NKR-2 study treatment administration.
during the study treatment until 3 weeks after first NKR-2 study treatment administration.

Dose-limiting toxicity refers to a specific adverse event that is experienced during treatment and until 3 weeks after first NKR-2 dose administration, is new and at least possibly related to NKR-2 study treatment administered following a preconditioning regimen

Secondary Endpoints
The NKR-2 cell kinetics endpoint of this Phase I study is: The evaluation of the circulating NKR-2 peripheral blood kinetics post-administration.
From day 1 (visit 4) until the end of the administration phase (day 85 = week 12 = Visit 22).
Additional Safety Endpoint: the occurence of Adverse Events ans Serious Adverse Events and any toxicity linked to study participation until the end of the administration phase, and until the end of the treatment follow-up
Until the end of the administration phase, and until the end of the treatment follow-up (at Month 24 - Visit 34).
Clinical activity secondary endpoints: The incidence of CR, CRMRD-, CRi, MLFS, PR, or SD for AML patients.
From week 5 until Month 24.
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelSEQUENTIAL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Phase I Dose Escalation Segment 1 - T7-DL1EXPERIMENTALPreconditioning (consisting in cyclophosphamide 300 mg/m² and fludarabine 30 mg/m² daily {CYFLU}) at days -9, -8 and -7. Dose 1: 1x108 NKR-2 (adjusted at 1.5x106 NKR-2/kg for patients with body weight ≤ 65 kg) administered at 7 days (T7) after the end of the preconditioning regimen
Phase I Dose Escalation Segment 1 - T3-DL1EXPERIMENTALPreconditioning (consisting in cyclophosphamide 300 mg/m² and fludarabine 30 mg/m² daily {CYFLU}) at days -5, -4 and -3. Dose 1: 1x108 NKR-2 (adjusted at 1.5x106 NKR-2/kg for patients with body weight ≤ 65 kg) administered at 3 days (T3) after the end of the preconditioning regimen
Phase I Dose Escalation Segment 1 - T3-DL2EXPERIMENTALPreconditioning (consisting in cyclophosphamide 300 mg/m² and fludarabine 30 mg/m² daily {CYFLU}) at days -5, -4 and -3. Dose 2: 3x108 NKR-2 (adjusted at 4.6x106 NKR-2/kg for patients with body weight ≤ 65 kg) administered at 3 days (T3) after the end of the preconditioning regimen
Phase I Dose Escalation Segment 1 - T3-DL3EXPERIMENTALPreconditioning (consisting in cyclophosphamide 300 mg/m² and fludarabine 30 mg/m² daily {CYFLU}) at days -5, -4 and -3. Dose 3: 1x109 NKR-2 (adjusted at 1.5x107 NKR-2/kg for patients with body weight ≤ 65 kg) administered at 3 days (T3) after the end of the preconditioning regimen
Phase I Dose Escalation - extensionEXPERIMENTALThis extension segment will enroll more patients (to reach 9 evaluable patients in total) to further evaluate the selected treatment regimen, i.e., the recommended NKR-2 dose (1x108 or 3x108 or 1x109NKR-2/injection) with the CYFLU preconditioning treatment administered at the recommended interval (T3 or T7) prior to NKR-2 administration.
Phase II Segment 1EXPERIMENTALThis extension segment will enroll more patients (to reach 13 evaluable patients in total) to further evaluate the selected treatment regimen, i.e., the recommended NKR-2 dose (1x108 or 3x108 or 1x109NKR-2/injection) with the CYFLU preconditioning treatment administered at the recommended interval (T3 or T7) prior to NKR-2 administration.
Phase II Segment 2EXPERIMENTALEnrollment in the Phase II part of the study will be divided in 2 consecutive segments, with 13 patients in total in the segment 1 and 30 new patients in segment 2 (43 patients in total) if the study is not terminated due to futility, according a Simon's two-stage optimal design
Interventions
NameTypeDescription
NKR-2BIOLOGICALThis Phase I study will explore the hypothesis that the administration of modified T-cells targeting NKG2D-ligands expressed by AML/MDS cells, after a prior nonmyeloablative preconditioning treatment, in patients refractory to and/or relapsing after prior therapies, is safe and, considering the poor outcomes and lack of therapeutic strategies for this patient population, may have a strategic advantage over current approaches and provide potential clinical benefit.
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Eligibility Criteria
Age Range18 Years — 70 Years
SexALL
Healthy VolunteersNo
Study Sites7

Inclusion Criteria: 1. The patient must have signed the written ICF and must accept that, beyond the treatment period, and the treatment follow-up period, he/she will have to be monitored for a Long-Term Safety Follow-Up (LTSFU) for up to 15 years after enrollment. 2. Both men and women of all race...

Countries:United StatesBelgium
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