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

NCT05218408 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: CYNK-001-GBM-002
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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)

Conditions

Astrocytoma, Grade IV; Glioblastoma; Giant Cell Glioblastoma; Glioblastoma Multiforme

Keywords

Interleukin-1; Cyclophosphamide; Fludarabine; immunosuppressive agents; immunological factor; IDH wild type; Surgical GBM; Natural Killer; Cellular Therapy; Allogeneic; Allogeneic stem cell; Ommaya catheter

Outcome Measures

Primary Outcomes (3)

• 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

  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

  42 days

• Phase IIa CYNK-001 efficacy

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

  6 Months

Secondary Outcomes (2)

• Phase 1-Progression free survival at 6 Months

  6 Months

• Overall survival phase I and IIa

  6,9 and 12 months

Other Outcomes (9)

• Progression Free survival Phase I and IIa

  9 and 12 months

• Median Progression Free Survival (mPFS) post tumor resection

  6, 9,12 , 18 and 24 months

• Median Overall Survival (mOS) post tumor resection

  12 and 24 months

Study Arms (2)

Phase 1Surgical rGBM CYNK-001 infusion ( IV and IC) in combination with IL-2

EXPERIMENTAL

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.

Biological: CYNK-001 systemic and Intra cavity administration

Phase IIa Surgical rGBM CYNK-001 at MPD IV and IC

EXPERIMENTAL

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

Biological: CYNK-001 systemic and Intra cavity administration

Interventions

CYNK-001 systemic and Intra cavity administration BIOLOGICAL

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 1Surgical rGBM CYNK-001 infusion ( IV and IC) in combination with IL-2; Phase IIa Surgical rGBM CYNK-001 at MPD IV and IC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be 18 years or older of age on the day of signing informed consent.
• Have had historical or current histologically confirmed isocitrate dehydrogenase 1(IDH1) wild-type glioblastoma and variants as defined by the World Health Organization
• Patient must have a T1 weighted 3D MRI with Gadolinium enhancement within 14 days prior to lymphodepletion at Day -5
• Patient must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Radiologically confirmed recurrent glioblastoma at first or second recurrence have contrast enhancing measurable disease with a bidimensional diameter greater than or equal to 10 mm x 10 mm according to RANO and be eligible to undergo tumor resection.
• Patients must be a candidate to undergo non-emergent surgical resection of the primary target lesion.
• Multifocal GBM is permissible in the study if there is contiguous T2FLAIR hyperintensity between enhancing lesions on T1 post gadolinium sequences and if in the opinion of the PI surgical resection of the multifocal disease is achievable.
• NOTE: Multicentric disease with no demonstrated ventricle communication at the time of screening is excluded.
• The patient must either be on no steroids or on a stable dose of dexamethasone or equivalent no greater than \> 2 mg a day for at least 5 days prior to lymphodepletion.
• Karnofsky performance status (KPS) ≥ 60
• Have washout periods for prior therapies defined as at five half-lives or (4 weeks) prior to the administration of lymphodepletion whichever is shorter
• Demonstrate at screening adequate organ function by laboratory values as follows:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelet count ≥ 100 x 10\^9/L (patient needs to have a minimum of 70 x10\^9/L to undergo resection)
• Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L

You may not qualify if:

• Midline shift greater than 0.5 cm or pending herniation.
• Patients who were previously treated with Bevacizumab. The use of Bevacizumab for edema or radiation necrosis treatments may be allowed with prior approval from the medical monitor
• Anticipated Extent of Resection by volumetric analysis is less than 70%
• Patients with greater than two recurrences of GBM are excluded
• Patients with any contraindications to MRIs
• Treatment with other investigational agents, check point inhibitors and prior immunotherapy such as Vaccine therapy, dendritic cells vaccine within 4 weeks prior to lymphodepletion.
• Prior radiation therapy within 12 weeks of screening MRI unless there is unequivocal histological confirmation of tumor progression.
• Patients with known disease in the posterior fossa, gliomatous meningitis, extracranial disease or multicentric enhancing disease. Multicentric disease is defined as discrete sites of contrast enhancing disease without contiguous T2/FLAIR abnormality.
• NOTE: Satellite lesions that are associated with a contiguous area of T2/FLAIR abnormality as the main lesion(s) may be included.
• Patients with concurrent use of tumor treating fields (TTF) or laser interstitial thermal therapy (LITT) is excluded. Prior use of TTF or LITT is allowed prior to signing the ICF
• Patients with current Carmustine wafers. (Patients that agree to remove the Carmustine wafers at the time of tumor resection during the study are allowed in the study)
• Patents who are receiving systemic steroid therapy \> 2 mg of dexamethasone or equivalent total dose per day or any other form of immunosuppressive therapy within 5 days of lymphodepletion.
• Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients requiring physiological doses of steroids (i.e., adrenal insufficiency or hypopituitarism) not to exceed equivalent of dexamethasone 2 mg will not be excluded from the study.
• Patients with history of anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome
• Active autoimmune disease other than controlled connective tissue disorder or those who are not on active therapy.

Sponsors & Collaborators

• Celularity Incorporated: lead

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Adrian Kilcoyne, MD

  Celularity inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 18, 2022
• First Posted: February 1, 2022
• Study Start: March 8, 2022
• Primary Completion: February 1, 2024
• Study Completion: May 1, 2024
• Last Updated: February 16, 2023

Record last verified: 2023-02