Nogapendekin Alfa-Inbakicept and iNKT Cells for Critically Ill Adults With Severe Community-Acquired Pneumonia (With or Without Sepsis/ARDS)

Phase 2 Study Evaluating Nogapendekin Alfa Inbakicept and iNKT Cells in Critically Ill Adults With Severe Community-Acquired Pneumonia With or Without Sepsis/Acute Respiratory Distress Syndrome.

This Phase 2 study tests whether adding two immune therapies - nogapendekin alfa-inbakicept (NAI) and off-the-shelf iNKT cell infusions - to standard care can safely help critically ill adults with severe community-acquired pneumonia (CAP) (with or without sepsis/ARDS) recover. The study will give NAI by subcutaneous injection (Days 1 and 10) and one IV dose of iNKT cells (Day 3), then follow participants for 90 days.

Study Overview

• Status: Withdrawn
• Conditions: Sepsis; Acute Respiratory Distress Syndrome; Severe Community-Acquired Pneum; Lymphopenia / Immunoparalysis in Critically Ill Adults
• Intervention / Treatment: Drug: Nogapendekin Alfa-Inbakicept (NAI); Drug: Allogeneic invariant Natural Killer T (iNKT) Cells (AgenT-797)

Detailed Description

Phase 2, single-arm study in up to 20 critically ill adults with severe community-acquired pneumonia (CAP) (with or without sepsis/ARDS) and lymphopenia (ALC <1,500/µL). The study evaluates the safety, tolerability, and preliminary efficacy of combining an IL-15 superagonist (nogapendekin alfa-inbakicept, NAI) with an allogeneic invariant natural killer T cell product (iNKT cells) added to standard ICU care.

Key elements

Population: Adults (≥18) admitted to ICU for severe CAP within 72 hours, meeting IDSA/ATS severe CAP criteria (≥1 major or ≥3 minor) and on antibiotics.

Planned enrollment: up to 20 participants (≈40 screened).

Intervention schedule:

Day 1: NAI subcutaneous (≤50 kg → 15 µg/kg; >50 kg → fixed 1 mg). Day 3: Single IV infusion of iNKT cells (1 × 10^9 cells). Day 10: Second NAI subcutaneous dose (same dosing as Day 1). Concomitant care: all participants receive guideline-based standard of care for CAP/sepsis/ARDS (antibiotics, organ support, lung-protective ventilation, vasopressors, low-dose steroids as indicated, etc.).

Safety oversight: continuous ICU monitoring; Sponsor Drug Safety review of SAEs; Safety Review Committee (SRC) reviews safety after first 5 participants and oversees stopping rules. Predefined toxicity rules and management algorithms for infusion reactions, CRS, and ICANS are specified.

Primary endpoints: safety/tolerability (TEAEs, SAEs, grade ≥3 AEs) and 28-day all-cause mortality.

Secondary endpoints: absolute lymphocyte count recovery, ventilator-free days, ICU-free days, antibiotic-free days, days free from organ support, time to ICU/hospital discharge, incidence of secondary infections through Day 28, and 90-day mortality.

Exploratory endpoints: serum cytokines, NK and T-cell expansion and activation/exhaustion markers, monocyte HLA-DR, quantification and persistence of donor iNKT cells (Days 1, 7, 14, 28).

Duration per participant: treatment up to 10 days; follow-up to 90 days after first dose.

Stopping/discontinuation: specified criteria for permanent discontinuation (e.g., drug-related Grade ≥3 organ toxicity, Grade ≥3 CRS/ICANS, intolerable infusion reactions), SRC stopping rules (including treatment-related death or clustered severe toxicities).

Objective: determine whether the NAI + iNKT combination can be given safely in this population and provide signals of reduced 28-day mortality and immune recovery (reversal of lymphopenia) to justify further study.

Sites will collect clinical outcomes, safety data, laboratory panels (CBC/CMP/coagulation), and samples for immune monitoring per protocol schedule.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria-

1. Age ≥ 18 years.

2. Critically ill adult requiring ICU admission due to severe community acquired pneumonia (CAP), defined by ≥1 major criterion or ≥3 minor criteria (IDSA/ATS):

   • Major: respiratory failure requiring mechanical ventilation OR septic shock requiring vasopressors.
   • Minor: tachypnea (RR ≥ 30), PaO2/FiO2 ≤ 200, multilobar infiltrates, new confusion/disorientation, BUN ≥ 20 mg/dL, platelet count < 100,000/µL, core temperature < 36.0°C, hypotension requiring aggressive fluid resuscitation.
3. Hospital admission with diagnosis of CAP within 72 hours.
4. Lymphopenia: absolute lymphocyte count (ALC) < 1,500/µL (not secondary to chemotherapy).
5. Receiving antibiotics for CAP (at least one dose since ICU admission).
6. Informed consent obtainable from participant or legally authorized representative.

Exclusion Criteria-

1. Hematologic malignancy (e.g., active leukemia or lymphoma not in remission).
2. Post CAR T therapy or hematopoietic cell transplant for ALL, NHL, or multiple myeloma < 3 months prior to enrollment.
3. Current diagnosis of cytokine release syndrome.
4. Receiving colony stimulating factors (e.g., G CSF).
5. Clinical history or imaging suggesting aspiration of gastric contents.
6. Advanced dementia or prolonged bedridden status.
7. Pregnancy or breastfeeding.
8. High dose immunosuppressive therapy at baseline (e.g., > 0.5 mg/kg prednisone or equivalent). (Low dose corticosteroids for septic shock/ARDS per SOC permitted.)
9. Uncontrolled autoimmune or inflammatory disease requiring immunosuppressive therapies.
10. Life expectancy < 24-48 hours or moribund condition despite care (investigator judgment).
11. Active uncontrolled bleeding or intracerebral hemorrhage.
12. Known hypersensitivity to ingredients used in the cell product formulation (e.g., DMSO).
13. Treated by antibiotics for the current respiratory infection for more than seven days at time of hospitalization (unless culture/sensitivity indicates resistant organism to administered antibiotics).
14. Known active viral hepatitis A, B, or C.
15. Investigator judgment that participation is not in the participant's best interest or participant is unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NAI Plus iNKT Cells With Standard of Care; Single-arm treatment: all participants receive nogapendekin alfa-inbakicept (NAI) plus a single infusion of allogeneic iNKT cells in addition to guideline-based standard of care. NAI SC on Day 1 and Day 10 (≤50 kg: 15 µg/kg; >50 kg: fixed 1 mg). iNKT cells IV single dose on Day 3 (1 × 10^9 cells). Standard ICU care (antibiotics, ventilation/organ support, vasopressors, low-dose steroids as indicated) provided per site. Continuous safety monitoring with SRC review after first 5 participants.

Drug: Nogapendekin Alfa-Inbakicept (NAI); Nogapendekin alfa-inbakicept (NAI) - a recombinant IL-15 superagonist complex (IL-15N72D:IL-15RαSu/IgG1 Fc) administered subcutaneously (Day 1 and Day 10; weight-based 15 µg/kg if ≤50 kg or fixed 1 mg if >50 kg) to stimulate NK and CD8+ T-cell proliferation and function.; Other Names: ALT-803; N-803; Anktiva; Drug: Allogeneic invariant Natural Killer T (iNKT) Cells (AgenT-797); Allogeneic invariant Natural Killer T (iNKT) Cells (AgenT-797) - cryopreserved, GMP-manufactured off-the-shelf donor iNKT cell product administered as a single intravenous infusion (1 × 10^9 cells on Day 3) intended to provide immediate effector function and immunomodulation; cell product thawed and infused per cell-therapy procedures with premedication as indicated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day all-cause mortality	Proportion of participants who die from any cause within 28 days of first study drug administration.	Day 28 (28 days after first dose)
Treatment Emergent Adverse Events (TEAEs)	Any new or worsening medical event beginning after the first dose through 30 days post-last dose, collected to characterize overall tolerability.	From first study treatment to 30 days after the participant's last study dose.
Severe Adverse Events (SAEs)	Events meeting regulatory seriousness criteria (death, life-threatening, hospitalization, disability, congenital anomaly or other medically important events) reported to evaluate major safety risks.	From first study treatment to 30 days after the participant's last study dose (SAEs related to study product reported regardless of last dose date).
Grade ≥3 TEAEs	Adverse events of CTCAE severity grade 3 or higher that emerge after first dose, used to quantify severe toxicity burden.	From first study treatment to 30 days after the participant's last study dose.
Safety laboratory tests	Routine clinical labs (CBC, chemistry, coagulation, etc.) collected serially to detect clinically meaningful laboratory abnormalities attributable to treatment.	From baseline (pre-dose) through 30 days after the participant's last study dose.
Temperature	Serial core body temperature measured in degrees Celsius. Report baseline, maximum post-dose within 24 hours, and incidence of fever >39.0°C.	Baseline (pre-dose) through End of ICU stay; intensified monitoring for 24 hours after iNKT infusion (vitals every ≥4 hours; continuous telemetry as indicated).
Heart rate	Serial heart rate (bpm). Report baseline, peak within 24 hours post-infusion, and incidence of new clinically significant tachycardia (>120 bpm) requiring intervention.	Baseline (pre-dose); maximum post-dose within 24 hours after iNKT infusion (intensified monitoring during this 24-hour window); overall reporting through End of ICU stay (up to 28 days).
Blood pressure	Serial systolic/diastolic blood pressure (mmHg). Report baseline, nadir within 24 hours post-infusion, and incidence of new hypotension (MAP <65 mmHg or need for new/increased vasopressor) temporally related to infusion.	Baseline (pre-dose); maximum post-dose within 24 hours after iNKT infusion (intensified monitoring during this 24-hour window); overall reporting through End of ICU stay (up to 28 days).
Respiratory rate	Serial RR (breaths/min). Report baseline, worst value within 24 hours post-infusion, and incidence of clinically significant tachypnea (RR ≥30) or new respiratory deterioration requiring escalation.	Baseline (pre-dose); maximum post-dose within 24 hours after iNKT infusion (intensified monitoring during this 24-hour window); overall reporting through End of ICU stay (up to 28 days).
Oxygen saturation	Serial peripheral oxygen saturation (%). Report baseline, nadir within 24 hours post-infusion, and incidence of new hypoxemia (SpO2 <90% on prior baseline support or increase in FiO2/ventilatory support).	Baseline through End of ICU stay; intensified monitoring for 24 hours after iNKT infusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Lymphocyte Count (ALC)	Peripheral ALC measured over time to evaluate reversal of lymphopenia and quantitative immune recovery after treatment.	Assessed at baseline and summarized at Days 7, 14, 21, and 28 after first dose.
Ventilator-free days (VFD) through Day 28	From first study treatment through Day 28 after first dose.	Number of days within the 28-day window the participant is alive and free from mechanical ventilation, with death or ventilator dependence to Day 28 scored as zero.
ICU-free days through Day 28	Number of days within 28 days the participant is alive and not in ICU, reflecting time free from intensive care support.	From first study treatment through Day 28 after first dose.
Antibiotic-free days through Day 28	Number of days within 28 days the participant is alive and not receiving systemic antibiotics for respiratory infection, as a proxy for infection control and clinical recovery.	From first study treatment through Day 28 after first dose.
Days alive and free of other organ support through Day 28	Count of days within 28 days the participant is alive and not requiring non-respiratory organ supports (eg, vasopressors, renal replacement therapy), reflecting multi-organ recovery.	From first study treatment through Day 28 after first dose.
Time to ICU discharge	Interval from first dose to date/time participant leaves ICU, used to assess speed of clinical improvement sufficient for lower-level care.	From first study treatment (Day 1) through Day 28 - time to ICU discharge will be reported as days from first dose to date/time of ICU discharge; participants not discharged by Day 28 will be censored at Day 28.
Time to hospital discharge	From first study treatment until hospital discharge (if occurs).	From first study treatment (Day 1) through Day 28 - time to hospital discharge will be reported as days from first dose to date of hospital discharge; participants not discharged by Day 28 will be censored at Day 28.
Number of secondary infections through Day 28	Incidence and timing of new clinically documented infections (eg, ventilator-associated pneumonia, bloodstream infection) occurring within 28 days, to evaluate infection risk post-treatment.	From first study treatment through Day 28 after first dose.
Number of secondary infections through participant follow-up	From first study treatment through 90 days after first dose.	Incidence of new clinically documented infections up to 90 days to capture later-onset infectious complications.
90-day all-cause mortality	Death from any cause occurring within 90 days of first treatment to evaluate longer-term survival.	From first study treatment to Day 90 after first dose.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum cytokines	Serial measurement of inflammatory and regulatory cytokines (eg, IL-6, IL-10, IFN-γ, IL-15) to characterize immune activation, resolution, or dysregulation in response to therapy.	Baseline and at Days 1, 7, 14, and 28 after first dose (or last available in-person visit).
NK cell expansion / T-cell activation-exhaustion markers / other immunologic parameters	Flow-cytometry and related assays quantifying NK and T-cell counts/phenotype (eg, Ki-67, PD-1) to assess cellular immune activation, proliferation, and exhaustion status post-treatment.	Baseline and Days 1, 7, 14, and 28 after first dose.
Percentage normalizing monocyte HLA-DR by Day 7 and Day 14 and change in HLA-DR expression	Proportion of participants achieving restoration of monocyte HLA-DR expression (a biomarker of innate immune competence) and magnitude of change from baseline.	Assessed at Days 7 and 14 after first dose.
Quantification of circulating iNKT cells (peak count) and persistence	Peak peripheral donor iNKT cell counts and duration of detectable donor cells to assess in vivo engraftment/ persistence of the infused product.	Measured at baseline and at Days 7, 14, and 28 after first dose.
Increase in NK cell count by Day 14	Change in NK cell absolute count at Day 14 versus baseline to evaluate early innate immune expansion attributable to NAI.	From baseline to Day 14 after first dose.

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2026
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): January 15, 2027

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 20, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: intensive care unit; critical care; immunotherapy; ICU; ARDS; cell therapy; sepsis; CAP; acute respiratory distress syndrome; lymphopenia; community-acquired pneumonia; immunoparalysis; ventilator-free days; iNKT cells; sepsis shock; immune monitoring; nogapendekin alfa-inbakicept; NAI; ANKTIVA; AgenT-797; IL-15 superagonist
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Immune System Diseases; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Lung Diseases; Respiration Disorders; Leukocyte Disorders; Hematologic Diseases; Immunologic Deficiency Syndromes; Pneumonia; Leukopenia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Community-Acquired Infections; Respiratory Distress Syndrome; Sepsis; Lymphopenia; Community-Acquired Pneumonia; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytological Techniques; Cell Physiological Phenomena; ALT-803; Cell Count
• Other Study ID Numbers: ResQ219-CAP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No