A Phase 1/2a Open Label Multicenter, Non-Randomized, Trial to Assess the Safety and Efficacy of CYNK-001 in Combination with Recombinant Human Interleukin-2 in Adults with Recurrent Resection Eligible IDH1 wild-type Glioblastoma. For phase I portion, the study objectives to assess the safety and feasibility CYNK-001 in combination with rhIL2 of Intravenous (IV) infusion and Intracavitary (IC) administrations following tumor resection and to establish a maximum tolerated dose (MTD) and a Recommended Phase 2a Dose (RP2D) for IV and IC CYNK-001 administration. For Phase IIa, to evaluate efficacy and safety of CYNK-001 administrations in recurrent GBM as measured by Progression Free Survival at 6 months (PFS6M)
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Phase 1 Lymphodepletion Days -5,-4 and -3 Cyclophosphamide 900 mg/m2, Fludarabine 30 mg/m2 and Mesna per SOC IL 2 at 6M IU subcutaneous administration: For IV cycle ( cycle1) rhIL2 will be administered on Days 1,3,5,8,9,11 and 15 . On days 1, 8 and 15 rhIL-2 will be administered 1 to 3 hours prior to CYNK-001 infusions For IC cycles rhIL2 will be administered 1 to 3 hours prior to each CYNK-001 IC dose. CYNK-001 : for IV at 2.4 x10\^9 or 3.6 x10\^9 cells Days 1,8 and 15 Tumor resection will take place 7 to 14 day follow by first IC cycle ( Cycle 2) at 100 Million cells or 200 Million cells IC cycles 3,4,5 once a week for three weeks , 28 days cycle at100 Million cells or 200 Million cells only for Phase 1 cohort 4 and Phase 2a
Phase I-Number of patients experience Dose limiting toxicity (DLT)
Defined as the maximum dose safely administered intravenously or Intracavitary for the treatment of patients with GBM
Time frame: 42 days
To establish maximum tolerated dose (MTD) and a Recommended Phase 2a Dose (RP2D)
Defined as the number of patients experience Adverse Events and severity
Time frame: 42 days
Phase IIa CYNK-001 efficacy
To evaluate CYNK-001 efficacy post tumor resection and survival within PFS6 Month
Time frame: 6 Months
Phase 1-Progression free survival at 6 Months
is defined as the time from the tumor resection to the date of first documented disease progression determined in accordance with RANO (and iRANO) or death due to any reason, whichever occurs first
Time frame: 6 Months
Overall survival phase I and IIa
is defined as the time from the tumor resection until the date of death at 6,9 and 12 months
Time frame: 6,9 and 12 months
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