Dendritic Cell Immunotherapy for Treatment of Adult GBM

Diakonos Oncology Corporation

Status and phase: Enrolling; Phase 2

Conditions: Glioblastoma (GBM)

Treatments: Drug: Temodar (Temozolomide); Biological: DOC1021; Radiation: SOC cranial radiation; Procedure: Tumor resection

Study type: Interventional

Funder types: Industry

Identifiers

NCT06805305

DOC-GBM2

Details and patient eligibility

About

The goal of this clinical trial is to learn if DOC1021 + pIFN alongside standard of care (SOC) will improve survival in adult patients newly diagnosed with glioblastoma (IDH-wt). It will also evaluate the safety of DOC1021 + pIFN. Researchers will compare DOC1021 dendritic cell immunotherapy regimen added to SOC compared to SOC treatment alone.

Participants in the DOC1021 + pIFN + SOC arm will:

• Take filgrastim subcutaneously x 5 doses and subsequently undergo a leukapheresis collection
• Undergo ultrasound guided perinodal DOC1021 injections every 2 weeks for a total of 3 doses
• Receive subcutaneous pIFN injections weekly for a total of 6 doses in parallel with the DOC1021 injections

Both arms of the trial will:

• Visit the clinic regularly to assess quality of life, symptoms, medication use, imaging, bloodwork, and to receive SOC treatment with surgery, temozolomide chemotherapy and radiation

Enrollment: 135 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Age 18 years or older

4. Presumed diagnosis of GBM deemed to be potentially resectable and deemed to be a good candidate for postoperative standard of care temozolomide and radiation therapy.

   1. The surgical objective is for gross total resection (GTR)/near-total resection (NTR) defined as greater than or equal to 95% of contrast enhancing (CE) tumor removed plus less than or equal to 1 cm3 residual CE tumor. Patients with subtotal resection will still be eligible if at least 70% of the CE tumor is resected.
   2. Eligibility will be confirmed after surgery when diagnosis of GBM IDH-wt confirmed prior to randomization.
   3. Patients with prior biopsy or subtotal resection are eligible if no other anti-cancer treatment received for glioblastoma and additional resection indicated.

5. Ability to receive filgrastim (e.g. Neupogen), leukapheresis and 3 bi-weekly injections of DOC1021 near deep cervical lymph nodes + weekly pIFN x 6 weeks.

6. Females of reproductive potential must have a negative serum pregnancy test and agree to use effective contraception (as determined appropriate for the patient by the investigator) during study treatment.

7. Adequate kidney, liver, bone marrow function, and immune function, as follows:

   1. Hemoglobin ≥ 8.0 gm/dL (use of transfusion or other intervention to achieve is acceptable)
   2. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
   3. Platelet count ≥ 75,000/mm3
   4. Calculated creatinine clearance (CrCl) > 30 mL/min using Cockcroft and Gault formula:

   i. For males = (140 - age[years]) x (body weight [kg]) / (72 x serum creatinine [mg/dL]) ii. For females = 0.85 x value from male formula e. Total bilirubin ≤ 1.5 times upper limit of normal (ULN) except in patients with Gilbert's disease for which total bilirubin must be ≤ 2 times ULN f. Aspartate transaminase AST (SGOT) and alanine aminotransferase ALT (SGPT) ≤ 3 times the ULN

8. Karnofsky Performance Score ≥ 70

Exclusion criteria

1. Multifocal, deep midline, infratentorial, recurrent, leptomeningeal or extracranial disease.
2. Patients who are pregnant or breastfeeding.
3. Known active HIV or hepatitis infection. Patients with HIV that is well-controlled and have undetectable viral titers remain eligible. Patients with history of HCV adequately treated such that RNA viral load is negative also remain eligible.
4. Any severe or uncontrolled medical condition or other condition that could affect participation in this study as determined by the investigator, including but not limited to uncontrolled or severe cardiac disease, systemic autoimmune disorders requiring immunosuppression in the past 2 years, autoimmune hyper/hypothyroidism, untreated vi-ral hepatitis, autoimmune hepatitis.
5. Treatment with another investigational drug or other experimental intervention within the last 30 days.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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135 participants in 2 patient groups

DOC1021 + pIFN + SOC

Experimental group

Description:

DOC1021 administered by injection near deep-cervical lymph nodes + pIFN adjuvant with standard of care treatment

Treatment:

Procedure: Tumor resection

Radiation: SOC cranial radiation

Biological: DOC1021

Drug: Temodar (Temozolomide)

SOC

Active Comparator group

Description:

Standard of Care treatment alone

Treatment:

Procedure: Tumor resection

Radiation: SOC cranial radiation

Drug: Temodar (Temozolomide)