A Phase 1b / 2 Drug Resistant Immunotherapy With Activated, Gene Modified Allogeneic or Autologous γδ T Cells (DeltEx) in Combination With Maintenance Temozolomide in Subjects With Recurrent or Newly Diagnosed Glioblastoma

NCT05664243 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: INB-400
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 5

Brief Summary

This multicenter, Phase 1b/2 study is being conducted to determine if the experimental cell therapy is safe, tolerable and can delay the return of cancer in patients with a newly diagnosed or recurrent glioblastoma multiforme (GBM) in combination with standard chemotherapy treatment temozolomide (TMZ). If there is a 25% or greater improvement in survival in this study then the therapy should be studied further.

Conditions

Glioblastoma

Keywords

Glioblastoma; Brain Neoplasms; Glioma; Neoplasms; Neuroepithelial; Central Nervous System Neoplasms; Neoplasms by Site

Outcome Measures

Primary Outcomes (4)

• Autologous Phase 2, Arm A in newly diagnosed glioblastoma: 12-month overall survival (OS) rate

  Date of first dose to date of death by any cause

  12 Months

• Allogeneic Phase 1b, establishes the recommended phase 2 dose (RP2D) for phase 2 allogeneic arms and subject or product characteristics that will optimize manufacturing

  \<30% dose limiting toxicity (DLT) observed with dose

  28 days

• Allogeneic Phase 2, Arm B confirmed recurrent glioblastoma, 9-month overall survival (OS)

  Date of first dose to date of death by any cause

  9 Months

• Allogeneic Phase 2, Arm C newly diagnosed glioblastoma, 12-month overall survival (OS) rate

  Date of first dose to date of death by any cause

  12 Months

Secondary Outcomes (6)

• Assessment of safety

  12 Months

• Assessment of tolerability

  12 Months

• Overall response rate (ORR)

  12 Months

• Time to progression (TTP)

  12 Months

• Progression free survival (PFS)

  12 Months

Study Arms (3)

1) Autologous Newly Diagnosed Disease: Phase 2 Arm A

EXPERIMENTAL

Arm A subjects with newly diagnosed disease will receive autologously derived, genetically modified gamma-delta T cells administered with maintenance temozolomide.

2) Allogeneic Relapsed Disease: Phase 1b and Phase 2

EXPERIMENTAL

Phase 1b subjects with relapsed disease will have allogeneic derived, genetically modified gamma-delta T cells administered with temozolomide

Biological: Allogeneic genetically modified gamma-delta T cells

3) Allogeneic Newly Diagnosed Disease: Phase 2 Arm C

EXPERIMENTAL

Arm C subjects with newly diagnosed disease will receive allogeneic derived, genetically modified gamma-delta T cells administered with maintenance temozolomide.

Interventions

Autologous genetically modified gamma-delta T cells BIOLOGICAL

Arm A: Cells will be administered on Day 1 of each of 6, 28-day cycles in combination with TMZ maintenance

Allogeneic genetically modified gamma-delta T cells BIOLOGICAL

Phase 1b and Arm B: Cells will be administered on Day 1 of each of 6, 28-day cycles in combination with D1 of TMZ 150mg/m2 Arms C: Cells will be administered on Day 1 of each of 6, 28-day cycles in combination with TMZ maintenance

2) Allogeneic Relapsed Disease: Phase 1b and Phase 2

Eligibility Criteria

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

You may qualify if:

• Subjects with histologically or cytologically confirmed history of IDH-wild type glioblastoma
• Phase 1b and Arm B of Phase 2: Subjects must have completed no more than one standard therapy for glioblastoma, have received no prior Avastin® therapy (unless solely used for edema management) and be eligible for resection
• Arms A and C: Subjects must have newly diagnosed, treatment naïve glioblastoma
• Phase 1b and Arm B and Arm C: Subjects must have a partially matched haploidentical or matched related donor.
• Subjects with magnetic resonance imaging (MRI) features consistent with and suspicious for recurrent malignant glioma in Phase 1b and Arm B.
• Agreeable to inserting and maintaining a Rickham catheter.
• ≥ 18 years of age.
• Karnofsky Performance Status ≥ 70%
• Female subjects of childbearing potential must have a negative urine/serum pregnancy test within 72 hours of study enrollment. Female subjects of childbearing potential are those who have not been surgically sterilized or have not been free of menses for \> 2 years.
• Male subjects and their female partners and female subjects of childbearing potential must be willing to use a combination of two methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study.

You may not qualify if:

• Subject in Arm A or donor from Phase 1b, Arms B, and Arm C received vaccinations within 4 weeks or underwent surgery (major or minor) within 72 hours before leukapheresis collection.
• Cellular immunotherapy or gene therapy or within six weeks prior to entering the study, surgical resection or alkylating agent chemotherapy within four weeks prior to entering the study, receiving tumor treating fields (TTF) Optune therapy, or have received experimental immunotherapy at any time
• Subjects receiving any other investigational agents concurrently while on study.
• Have not recovered from adverse events (≤ Grade 1) from previously administered therapy. Subjects with alopecia unless of immune origin are an exception to this criterion and may qualify for this study
• Have received prior treatment with an allogeneic therapy, including bone marrow or solid tumor transplant.
• Concurrent malignancy or an active second malignancy. Subjects with a history of second malignancy must have no evidence of cancer for two years prior to enrolment or have a surgically cured cancer with low risk of recurrence to enroll. Discuss with medical monitor prior to enrolment.
• Contraindication to the placement of an intracranial access device (Rickham catheter) at the time of surgery.
• Prior history of encephalitis, multiple sclerosis, or other CNS infection \<1 year prior to glioblastoma diagnosis.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, or any other medical condition that precludes surgery. Also, medical/surgical/psychiatric illness/social situations that would limit compliance with study requirements or confound interpretation of safety and efficacy data. Subjects with a history of seizure as a result of their glioblastoma must be seizure free and on appropriate anti-epileptic medication for 3 weeks prior to dosing with the investigational agent.
• Allergies/hypersensitivity to amino bisphosphonates such as Zoledronate®, Pamidronate® or similar.
• History of HIV or active hepatitis even if well controlled or history of an autoimmune condition.

Sponsors & Collaborators

• In8bio Inc.: lead

Study Sites (5)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Louisville Hospital/James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University Wexner Medical Center- James Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Zhao Y, Dong P, He W, Zhang J, Chen H. gammadelta T cells: Major advances in basic and clinical research in tumor immunotherapy. Chin Med J (Engl). 2024 Jan 5;137(1):21-33. doi: 10.1097/CM9.0000000000002781. Epub 2023 Aug 18.

  PMID: 37592858 DERIVED

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Glioma; Neoplasms; Central Nervous System Neoplasms; Neoplasms by Site

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Louis B Nabors, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Arm A subjects with newly diagnosed disease will receive autologously derived, genetically modified gamma-delta T cells administered with maintenance temozolomide. Phase 1b and Arm B subjects with relapsed disease will have allogeneic derived, genetically modified gamma-delta T cells administered with temozolomide Arm C subjects with newly diagnosed disease will receive allogeneic derived, genetically modified gamma-delta T cells administered with maintenance temozolomide.

Study Record Dates

• First Submitted: December 9, 2022
• First Posted: December 23, 2022
• Study Start: September 8, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 1, 2025

Record last verified: 2024-10

Locations

US (5)