N-803 and PD-L1 t-haNK Combined With Bevacizumab for Recurrent or Progressive Glioblastoma

NCT06061809 | Recruiting Phase 2 FDA Drug

• 1 other identifier: QUILT-3.078
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 4

Brief Summary

This study consists of 2 portions. The phase 2 portion is an open-label, single-arm study to evaluate the safety and efficacy of NAI, PD-L1 t-haNK, and bevacizumab combination therapy in participants with recurrent or progressive GBM. The phase 2B portion is an open-label, randomized study to evaluate the efficacy and safety for the following 2 experimental arms in participants with recurrent or progressive GBM: NAI, bevacizumab, and TTFields combination therapy (Arm A) or NAI, PD-L1 t-haNK, bevacizumab, and TTFields combination therapy (Arm B). Phase 2 Treatment for all enrolled participants will consist of repeated cycles of 28 days for a maximum treatment period of 76 weeks (19 cycles) as follows: Every 2 weeks (Days 1 and 15 of a 28-day cycle) Fourteen (14) participants were enrolled in the phase 2 portion of this study as of the date of this v02 protocol. No additional participants will be administered therapy in phase 2. Phase 2B Participants will be randomized 1:1 to 1 of 2 experimental arms (Arm A or Arm B). Treatment for all enrolled participants will consist of repeated 8-week cycles for a maximum treatment period of up to 80 weeks (10 cycles). Experimental Arm (A): Every 2 weeks (Days 1, 15, 29, and 43 of an 8-week cycle) Up to twenty (20) participants will be randomized in phase 2B (up to 10 participants/arm. Duration of Treatment: Participants will receive study treatment for up to 76 weeks during phase 2 (up to 19 repeated 28-day cycles) and for up to 80 weeks (up to 10 repeated 8-week cycles) during phase 2B or until they report unacceptable toxicity (not corrected with dose reduction), withdraw consent, or if the Investigator feels it is no longer in the participant's best interest to continue treatment. Treatment may also be discontinued if the participant has confirmed PD per iRANO, unless the participant is clinically stable and is considered potentially deriving benefit per Investigator's assessment. Duration of Follow-up: Participants who discontinue study treatment should remain in the study for follow-up. Participants should be followed for collection of survival status, posttreatment therapies (phase 2 and phase 2B), and medical history (phase 2B only) every 12 weeks (± 2 weeks) for the first 2 years then yearly thereafter for an additional 3 years. The maximum duration of follow-up is 5 years (260 weeks).

Conditions

Glioblastoma

Keywords

Progressive Glioblastoma; Recurrent Glioblastoma; N-803; ALT-803; PD-L1 t-haNK; Immunotherapy; Bevacizumab; Glioblastoma

Outcome Measures

Primary Outcomes (12)

• Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

  TEAEs and SAEs graded using the NCI CTCAE v5.0

  From beginning of Cycle 1 (each cycle is 28 days) to 30 days after end of treatment study visit.

• Incidence of clinically significant changes in comprehensive metabolic panel (CMP)

  Standard blood chemistry panel made up of 14 separate chemistry measurements so can detect a range of abnormalities in blood sugar, nutrient balance, and liver and kidney health. Each clinical site will use their local laboratory upper limit of normal (ULN) range. The treating investigator will assess each result composing the CMP and determine if each result is within expected normal range or outside of the expected normal range.

  From baseline, pre-intervention, Cycle 1 (each cycle is 28 days) and each subsequent treatment Cycle on Days 1 and Day 15 and at the end of treatment study visit.

• Incidence of clinically significant changes in Hematology blood panel.

  Blood test checking the levels for White Blood Cell, Red Blood Cell, Platelets, Hemoglobin, Hematocrit, Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils per unit volume. Each clinical site will use their local laboratory upper limit of normal (ULN) range. The treating investigator will assess each component of the Hematology panel and determine if each result is within expected normal range or outside of the expected normal range.

  From baseline, pre-intervention, Cycle 1 (each cycle is 28 days) and each subsequent treatment Cycle on Days 1 and Day 15 and at the end of treatment study visit.

• Incidence of clinically significant changes in Urinalysis.

  Checking the appearance, concentration and content of urine for any abnormalities. Each clinical site will use their local laboratory upper normal limit (UNL) range. The treating investigator will assess each component of the urinalysis and determine if each result is within expected normal range or outside of the expected normal range.

  From baseline, pre-intervention, Cycle 1 (each cycle is 28 days) and each subsequent treatment Cycle on Days 1 and Day 15 and at the end of treatment study visit.

• 12-lead Electrocardiogram (ECG)

  Perform 12-lead ECG as safety monitoring measurement. The parameters to be assessed for each one are the following: QT Interval, QTc Interval, QTcB Interval, QTcF Interval, PR Interval, QRS Duration and RR Interval with the unit in msec.

  From baseline, pre-intervention, Cycle 1 (each cycle is 28 days) and each subsequent Cycle Day1 through to the end of treatment study visit.

• Incidence of clinically significant changes in Temperature

  Temperature measured in either Fahrenheit or Celsius and for any abnormalities. Each site will assess to determine if temperature is within expected normal range or outside of the expected normal range.

  From baseline, pre-intervention, Cycle 1 (each cycle is 28 days) and Cycle 2 on days 1, 2 and 15, followed by each subsequent treatment Cycle on Days 1 and 15 and on the end of treatment study visit.

• Incidence of clinically significant changes in Heart Rate

  Heart rate measured in beats/minute. Each site will assess to determine if heart rate is within expected normal range or outside of the expected normal range.

  From baseline, pre-intervention, Cycle 1 (each cycle is 28 days) and Cycle 2 on days 1, 2 and 15, followed by each subsequent treatment Cycle on Days 1 and 15 and on the end of treatment study visit.

• Incidence of clinically significant changes in Respiratory Rate

  Respiratory rate measured in breaths/minute. Each site will assess to determine if respiratory rate is within expected normal range or outside of the expected normal range.

  From baseline, pre-intervention, Cycle 1 (each cycle is 28 days) and Cycle 2 on days 1, 2 and 15, followed by each subsequent treatment Cycle on Days 1 and 15 and on the end of treatment study visit.

• Incidence of clinically significant changes in Blood Pressure

  Blood pressure measured in Systolic and Diastolic mmHg. Each site will assess to determine if blood pressure is within expected normal range or outside of the expected normal range.

  From baseline, pre-intervention, Cycle 1 (each cycle is 28 days) and Cycle 2 on days 1, 2 and 15, followed by each subsequent treatment Cycle on Days 1 and 15 and on the end of treatment study visit.

• Incidence of clinically significant changes in Oxygen Saturation

  A pulse oximeter measures oxygen saturation as a percentage. Determines the ratio of the current levels of oxygenated hemoglobin to deoxygenated hemoglobin. Each site will assess to determine if oxygen saturation is within expected normal range or outside of the expected normal range.

  From baseline, pre-intervention, Cycle 1 (each cycle is 28 days) and Cycle 2 on days 1, 2 and 15, followed by each subsequent treatment Cycle on Days 1 and 15 and on the end of treatment study visit.

• Neurological assessment to grade Immune effector cell-associated neurotoxicity syndrome (ICANS)

  Using a 10-point immune effector cell encephalopathy \[ICE\] score for the grading of ICANS. A score of 10 represents no impairment, 7-9 score is grade 1 ICANS, 3-6 score is grade 2 ICANS, 0-2 score is grade 3 ICANS and finally grade 4 ICANs is where cannot perform assessment of tasks.

  On Cycle 1 (each cycle is 28 days) Day1, Day2, Day 15 and Day16, followed by each subsequent treatment Cycle on Days 1 and 15. Collection stops at the end of treatment study visit.

• Safety assessed by Cytokine Levels

  The safety cytokine levels are TNF-α and IL-6

  From Cycle 1 (each cycle is 28 days) Day1, Day2, Day 15 and Day16, followed by each subsequent treatment Cycle on Day 1. Collection stops at the end of treatment study visit.

Secondary Outcomes (4)

• Concentration of N-803 Pharmacokinetic (PK)

  On Cycle 1 (each cycle is 28 days) and Cycle 3 on treatment days 1, 2, 3, 4, 5 and 8.

• Concentration of PD-L1 t-haNK Pharmacokinetic (PK)

  On Cycle 1 (each cycle is 28 days) and Cycle 3 on treatment days 1, 2, 3, 4, 5 and 8.

• Detection of Immunogenicity of N-803

  On Cycle 1 (each cycle is 28 days) Cycle 2 on treatment days 1 and 15, followed by Cycle 7 Day 1 and at the End of Treatment study visit.

• Detection of Immunogenicity of PD-L1 t-haNK

  On Cycle 1 (each cycle is 28 days) Cycle 2 on treatment days 1 and 15, followed by Cycle 7 Day 1 and at the End of Treatment study visit.

Study Arms (3)

Single Arm

EXPERIMENTAL

Phase 2 Participants will receive N-803 1 mg subcutaneously (SC), PD-L1 t-haNK (\~2 × 10\^9 cells/infusion) intravenously (IV), and Bevacizumab (10 mg/kg IV) combination therapy during 28-day cycles on days 1 and 15 of each cycle. Maximum treatment period is 76 weeks, 19 cycles.

Drug: Bevacizumab; Drug: PD-L1 t-haNK; Drug: N-803

Experiment Treatment Arm A

EXPERIMENTAL

Phase 2B: Participants will be randomized 1:1 to 1 of 2 experimental arms (Arm A or Arm B). Treatment for all enrolled participants will consist of repeated 8-week cycles for a maximum treatment period of up to 80 weeks (10 cycles). Experimental Arm (A): Every 2 weeks (Days 1, 15, 29, and 43 of an 8-week cycle): N-803, 1 mg SC Bevacizumab, 10 mg/kg IV Continuous application (≥ 18 hours/day) to the brain: TTFields, 200 kHz

Drug: Bevacizumab; Drug: N-803; Device: Tumor Treating Fields (TTFields, 200 kHz)

Experiment Treatment Arm B

EXPERIMENTAL

Participants will be randomized 1:1 to 1 of 2 experimental arms (Arm A or Arm B). Treatment for all enrolled participants will consist of repeated 8-week cycles for a maximum treatment period of up to 80 weeks (10 cycles). Every 2 weeks (Days 1, 15, 29, and 43 of an 8-week cycle): PD-L1 t-haNK, 2 × 109 cells per infusion IV NAI, 1 mg SC Bevacizumab, 10 mg/kg IV Plus - Continuous application (≥ 18 hours/day) to the brain: TTFields, 200 kHz

Drug: Bevacizumab; Drug: PD-L1 t-haNK; Drug: N-803; Device: Tumor Treating Fields (TTFields, 200 kHz)

Interventions

Bevacizumab DRUG

Participants will receive 10mg/kg of Bevacizumab intravenously (IV) on Day 1 and Day 15 of each repeated cycle of treatment.

Also known as: Avastin

Experiment Treatment Arm A; Experiment Treatment Arm B; Single Arm

PD-L1 t-haNK DRUG

Participants will receive PD-L1 t-haNK (\~2 × 109 cells/infusion) intravenously (IV) on Day 1 and Day 15 of each repeated cycle of treatment.

Experiment Treatment Arm B; Single Arm

N-803 DRUG

Participants will receive 1mg subcutaneously (SC) on Day 1 and Day 15 of each repeated cycle of treatment.

Also known as: ALT-803, Anktiva

Experiment Treatment Arm A; Experiment Treatment Arm B; Single Arm

Tumor Treating Fields (TTFields, 200 kHz) DEVICE

TTFields (OPTUNE Gio®), for the treatment of newly diagnosed and/or recurrent GBM, is a portable battery or power supply operated device which produces alternating electrical fields, called tumor treatment fields ("TTFields") within the human body/brain. TTFields are applied to the patient by electrically-insulated surface transducer arrays. TTFields disrupt the rapid cell division exhibited by cancer cells. TTFields is comprised of two main components: (1) an Electric Field Generator and (2) INE Insulated Transducer Arrays (the transducer arrays). Patients carry the device in an over-the-shoulder bag or backpack and receive continuous treatment without changing their daily routine.

Experiment Treatment Arm A; Experiment Treatment Arm B

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
• Histologically-confirmed glioblastoma in accordance with the 2021 WHO Classification of Tumors of the CNS (WHO CNS5) that has progressed after initial therapy or therapies. The digital image to be provided for confirmation of histology by the Sponsor. Gliosarcoma, small cell GBM or other GBM variants, and molecular GBM are allowed.
• Progressive or recurrent disease will be confirmed (i.e. contrast enhanced magnetic resonance imaging (MRI) performed within 3 weeks prior to study treatment per RANO criteria or diagnostic biopsy).
• Previous first line treatment with at least radiotherapy and temozolomide. Subjects must have been off prior treatment at least 28 days prior to initiation of study therapy. Subjects must be at least 90 days from completion of radiation to reduce the risk of pseudoprogression being misdiagnosed as progression, unless the recurrence is a new enhancement on MRI outside the radiation treatment field or progression is confirmed by biopsy.
• Subjects must have recovered from prior treatment-related toxicities to Grade 2 or less.
• Life expectancy \> 12 weeks.
• Karnofsky Performance Status ≥ 70.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 6 months after completion of therapy, and non-sterile male subjects must agree to use a condom for up to 6 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and abstinence.
• Craniotomy must be adequately healed (at least 28 days between study treatment initiation and surgery).

You may not qualify if:

• Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drugs used in this study or that would put the subject at high risk for treatment related complications.
• Prior anticancer treatment of glioblastoma with bevacizumab or other anti-angiogenic treatment.
• Current chronic daily treatment (continuous for \> 3 months) with systemic corticosteroids (dose equivalent to or greater than 8 mg/day dexamethasone), excluding inhaled steroids. Short-term steroid use to prevent intravenous (IV) contrast allergic reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
• History of surgery in the past 28 days or with surgical wound not healed.
• History of serious hemorrhage as defined by NCI CTCAE 5.0 grading.
• Evidence of \> Grade 1 CNS hemorrhage on the baseline MRI scan.
• History of recent hemoptysis.
• Subjects receiving therapeutic anticoagulation.
• Subjects with a history or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding.
• Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease) requiring any treatment within the last 5 years.
• History of organ transplant requiring immunosuppression.
• History of active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
• Body weight ≤ 40 kg at screening.
• Inadequate organ function, evidenced by the following laboratory results:

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (4)

Chan Soon-Shiong Institute for Medicine (CSSIFM)

El Segundo, California, 90245, United States

NOT YET RECRUITING

Providence Medical Foundation

Fullerton, California, 92835, United States

RECRUITING

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

RECRUITING

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Bevacizumab; ALT-803

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Raymond Atiata

CONTACT

281.818.9921; Raymond.Atiata@immunitybio.com

Mark Nelson

CONTACT

Mark.Nelson@Immunitybio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: September 29, 2023
• Study Start: August 7, 2024
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: February 12, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)