Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Immunologic Factors

Immunosuppressive Agents

Interleukin-2

Mesna

Phase 1 dose escalation will utilize a 3+3 dose escalation design and will evaluate safety, feasibility, and preliminary efficacy of four cohort dose levels of CYNK-001 administered after a 6M IU subcutaneous dose of rhIL-2 for both IV and IC cycles. Up to 21 patients will be enrolled over 4 dosing cohorts in Phase 1.

To evaluate efficacy and safety of CYNK-001 administrations in recurrent GBM at maximum tolerated dose for IV and IC per Phase 1 outcome. No patients staggering will be implemented in phase 2a. DMC will review the phase 2a entirely

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

CYNK-001 systemic and Intra cavity administration

Adrian Kilcoyne, MD

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)

The study will contain two phases for the following objectives •The Phase 1 Dose Escalation will utilize a 3+3 dose escalation design and will evaluate safety, feasibility, and preliminary efficacy of four cohort dose levels of CYNK-001 administered after a 6M IU subcutaneous dose of rhIL-2 for both IV and IC cycles. Up to 21 patients will be enrolled over 4 dosing cohorts in Phase1 and 45 patients enrolled for phase IIa. Cohort 4 will be the safety run for Phase IIa. Cohort 4 in its entirety will be reviewed by the DMC prior to starting Phase 2a portion of this study. Phase 2a will continue to explore efficacy and safety of CYNK-001 in combination with rhIL2 in patients with recurrent resection eligible IDH1 wild-type glioblastoma.

CYNK-001 IV and IC in Combination With IL2 in Surgical Eligible Recurrent GBM With IDH-1 Wild Type

A Phase I/IIa Open Label Multicenter, Non-Randomized, Trial to Assess the Safety and Efficacy of CYNK-001in Combination With Recombinant Human Interleukin-2 in Adults With Recurrent Resection Eligible IDH1 Wild-type Glioblastoma

is defined as the time from the tumor resection until the date of death 9 and 12 months (PFS9 and PFS12) post tumor resection

is defined as the median 95% CIs time from the tumor resection until the date of death 9 and 12 months (PFS9 and PFS12) post tumor resection

is defined as the median as the 95%CI time from the tumor resection until the date of death.

is defined as the time from the tumor resection to the date of first documented disease progression determined in accordance with RANO(iRANO).

Defined as the proportion of subjects with best overall response of either complete response (CR) or partial response (PR)

To assess patient quality of life at baseline and post tumor resection surgery per the schedule of Events using EORTC QLQ C30 and EORTC QLQ BN 20 scale

NANO scale provides an objective clinician-reported outcome of neurologic function with high inter-observer agreement

any event not present prior to the initiation of the drug treatment

any untoward or unfavorable medical occurrence in patient during the clinical trial

Defined as the maximum dose safely administered intravenously or Intracavitary for the treatment of patients with GBM

Defined as the number of patients experience Adverse Events and severity

To evaluate CYNK-001 efficacy post tumor resection and survival within PFS6 Month

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

is defined as the time from the tumor resection until the date of death at 6,9 and 12 months

Celularity Incorporated

Nervous System Diseases

Substance Related Disorders

Neuroleptic Malignant Syndrome

Temozolomide

Poly(ADP-ribose) Polymerase Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Phase 1 Dose Escalation: All patients will receive NMS-03305293 and temozolomide (TMZ) administered orally (NMS-03305293 once or twice daily on days 1-7 or 28 consecutive days from Day 1 to Day 28; TMZ once daily on days 1-5;) in repeated 4-week cycles aimed at defining the Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Doses (RP2Ds) of NMS-03305293 in combination with TMZ. Each cycle is 28 days.

Phase 2: Once the RP2D is defined, the patients will receive TMZ daily on days 1-5 in combination with NMS-03305293 at the RP2D on days 1-7 or on days 1-28 every 28 days.

Backfill cohorts: additional patients may be treated with TMZ daily on days 1-5 and NMS-03305293 at different dose levels/schedules that have been previously assessed and determined to be safe, in order to properly characterize the exposure relationship over a range of doses/schedules. The backfill cohorts may run in parallel.

NMS-03305293

Route of administration: Oral

Commercially available temozolomide

Domenico Roberti

Multicenter, open-label, single-arm Phase 1/2 study on the safety and efficacy of the combination of NMS-03305293 and temozolomide (TMZ) in adult patients with diffuse gliomas (Phase 1) and isocitrate dehydrogenase (IDH) wild type glioblastoma (Phase 2) at first relapse.

Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma

A Phase I/II Combination Study of NMS-03305293 and Temozolomide in Adult Patients With Recurrent Glioblastoma

Objective Response Rate (ORR), calculated as the proportion of evaluable patients who have achieved, as best overall response (BOR), confirmed complete response (CR) or partial response (PR) through central retrospective assessment of RANO criteria

Safety will be assessed by adverse events (AEs), which include clinically significant abnormalities identified during a medical test (e.g. laboratory tests, electrocardiogram, vital signs, physical examinations). AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA) and their severity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).The analysis will focus on the events reported after the start of treatment (treatment emergent adverse events).

Plasma samples will be collected and used for pharmacokinetics assessments

Urine samples will be collected in patients treated in the phase 1 and in backfill cohorts and used for pharmacokinetics assessments

Complete and partial responses will be assessed according to RANO criteria

Duration of response will be calculated from the date of either first CR or PR until the date of documented progression for patients who achieved CR or PR. Patients who died without report of progression will be considered non-events and censored at their last disease-free assessment date

Progression Free Survival will be calculated from the date of treatment initiation to the date of first documentation of disease progression, or death due to any cause, whichever occurs first

Percentage of patients progressive-free at 6 months from treatment initiation

Percentage of patients alive at 9 and 12 months from treatment initiation.

Overall Survival will be calculated from the date of treatment initiation to the date of death due to any cause

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CYNK-001 IV and IC in Combination With IL2 in Surgical Eligible Recurrent GBM With IDH-1 Wild Type	NCT05218408	Astrocytoma, Gr... Glioblastoma Giant Cell Glio... Glioblastoma Mu...	CYNK-001 system...	18 Years -	Celularity Incorporated
Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma	NCT04910022	Glioblastoma Diffuse Glioma	NMS-03305293 Temozolomide	18 Years -	Nerviano Medical Sciences
Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma	NCT04910022	Glioblastoma Diffuse Glioma	NMS-03305293 Temozolomide	18 Years -	Nerviano Medical Sciences
CYNK-001 IV and IC in Combination With IL2 in Surgical Eligible Recurrent GBM With IDH-1 Wild Type	NCT05218408	Astrocytoma, Gr... Glioblastoma Giant Cell Glio... Glioblastoma Mu...	CYNK-001 system...	18 Years -	Celularity Incorporated

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