Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
PD-L1 t-haNK · 3 trials · 10 indications
TEAEs and SAEs graded using the NCI CTCAE v5.0
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The safety cytokine levels are TNF-α and IL-6
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECISTv1.1 criteria.
Maximum tolerated dose or highest tested dose and recommended phase 2 dose.
Incidence of DLTs and treatment-emergent adverse events (AEs) and serious AEs (SAEs), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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 |
| 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 |
| Dose Level 0: PD-L1 t-haNK + NAI + Cetuximab | EXPERIMENTAL | Dose level modifications of PD-L1 t-haNK and NAI due to toxicities will follow protocol specifications, starting at Dose Level 0 and de-escalating to Dose Level -1. Participants will complete: * Baseline visit. * Imaging scans every 8 weeks while on study. * Cycle 1 through End of Treatment: --Days 1 and 15 of 28 day cycle in the following order: Predetermined dose of PD-L1 t-haNK 1x daily, predetermined dose of NAI 1x daily, and predetermined dose of Cetuximab 1x daily. * End of Treatment visit with assessments. * Follow up: follow up every 3-4 months for up to 3 years after end of treatment. Longer-term follow-up every 6-12 months for up to 15 years. |
| Dose Level -1: PD-L1 t-haNK + NAI + Cetuximab | EXPERIMENTAL | Dose level modifications of PD-L1 t-haNK and NAI due to toxicities will follow protocol specifications. Participants will complete: * Baseline visit. * Imaging scans every 8 weeks while on study. * Cycle 1 through End of Treatment: --Days 1 and 15 of 28 day cycle in the following order: Predetermined dose of PD-L1 t-haNK 1x daily, predetermined dose of NAI 1x daily, and predetermined dose of Cetuximab 1x daily. * End of Treatment visit with assessments. * Follow up: follow up every 3-4 months for up to 3 years after end of treatment. Longer-term follow-up every 6-12 months for up to 15 years. |
| PD-L1 t-haNK Dose Level 1 | EXPERIMENTAL | PD-L1 t-haNK will be administered to patients with locally advanced or metastatic solid cancers. Planned number of subjects to be enrolled into Dose Level 1 is 3 to 6. |
| PD-L1 t-hanK Dose Level 2 | EXPERIMENTAL | PD-L1 will be administered to patients with locally advanced or metastatic solid cancers. Planned number of subjects to be enrolled into Dose Level 2 is 3 to 6. |
| PD-L1 t-haNK Dose Level Recommended phase 2 dose (RP2D) | EXPERIMENTAL | PD-L1 will be administered to patients with locally advanced or metastatic solid cancers. Planned number of subjects to be enrolled into RP2D is 4. |
| PD-L1 t-haNk Dose -1a (if needed) | EXPERIMENTAL | PD-L1 will be administered to patients with locally advanced or metastatic solid cancers. Planned number of subjects to be enrolled into Dose Level -1a is 3 to six, if needed. |
| Name | Type | Description |
|---|---|---|
| Bevacizumab | DRUG | Participants will receive 10mg/kg of Bevacizumab intravenously (IV) on Day 1 and Day 15 of each repeated cycle of treatment. |
| 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. |
| N-803 | DRUG | Participants will receive 1mg subcutaneously (SC) on Day 1 and Day 15 of each repeated cycle of treatment. |
| 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. |
| Cetuximab | DRUG | Epidermal growth factor receptor, via intravenous (into the vein) infusion per institutional standard of care. |
| NAI | BIOLOGICAL | Recombinant human superagonist, via subcutaneous injection (under the skin) per protocol. |
Phase 2 Inclusion Criteria: 1. Age ≥ 18 years. 2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines. 3. Histologically-confirmed glioblastoma in accordance with the 2021 WHO Classification of Tumors of the CNS (WHO CNS5) that has progressed af...
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