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

NCT07492888 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: ResQ219-CAP
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Sepsis; Acute Respiratory Distress Syndrome; Severe Community-Acquired Pneum; Lymphopenia / Immunoparalysis in Critically Ill Adults

Keywords

nogapendekin alfa-inbakicept; NAI; ANKTIVA; iNKT cells; AgenT-797; IL-15 superagonist; cell therapy; immunotherapy; community-acquired pneumonia; CAP; sepsis; sepsis shock; acute respiratory distress syndrome; ARDS; lymphopenia; immunoparalysis; intensive care unit; ICU; critical care; ventilator-free days; immune monitoring

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (10)

• Absolute Lymphocyte Count (ALC)

  Assessed at baseline and summarized at Days 7, 14, 21, and 28 after first dose.

• Ventilator-free days (VFD) through Day 28

  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

  From first study treatment through Day 28 after first dose.

• Antibiotic-free days through Day 28

  From first study treatment through Day 28 after first dose.

• Days alive and free of other organ support through Day 28

  From first study treatment through Day 28 after first dose.

Other Outcomes (5)

• Serum cytokines

  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

  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

  Assessed at Days 7 and 14 after first dose.

Study Arms (1)

NAI Plus iNKT Cells With Standard of Care

EXPERIMENTAL

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); Drug: Allogeneic invariant Natural Killer T (iNKT) Cells (AgenT-797)

Interventions

Nogapendekin Alfa-Inbakicept (NAI) DRUG

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.

Also known as: Anktiva, N-803, ALT-803

NAI Plus iNKT Cells With Standard of Care

Allogeneic invariant Natural Killer T (iNKT) Cells (AgenT-797) DRUG

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.

NAI Plus iNKT Cells With Standard of Care

Eligibility Criteria

• Age: 18 Years - 105 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• 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.
• Hospital admission with diagnosis of CAP within 72 hours.
• Lymphopenia: absolute lymphocyte count (ALC) \< 1,500/µL (not secondary to chemotherapy).
• Receiving antibiotics for CAP (at least one dose since ICU admission).
• Informed consent obtainable from participant or legally authorized representative.

You may not qualify if:

• Hematologic malignancy (e.g., active leukemia or lymphoma not in remission).
• Post CAR T therapy or hematopoietic cell transplant for ALL, NHL, or multiple myeloma \< 3 months prior to enrollment.
• Current diagnosis of cytokine release syndrome.
• Receiving colony stimulating factors (e.g., G CSF).
• Clinical history or imaging suggesting aspiration of gastric contents.
• Advanced dementia or prolonged bedridden status.
• Pregnancy or breastfeeding.
• 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.)
• Uncontrolled autoimmune or inflammatory disease requiring immunosuppressive therapies.
• Life expectancy \< 24-48 hours or moribund condition despite care (investigator judgment).
• Active uncontrolled bleeding or intracerebral hemorrhage.
• Known hypersensitivity to ingredients used in the cell product formulation (e.g., DMSO).
• 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).
• Known active viral hepatitis A, B, or C.
• Investigator judgment that participation is not in the participant's best interest or participant is unsuitable for enrollment.

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

MeSH Terms

Conditions

Respiratory Distress Syndrome; Sepsis; Lymphopenia; Community-Acquired Pneumonia

Interventions

ALT-803; Cell Count

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Immunologic Deficiency Syndromes; Immune System Diseases; Community-Acquired Infections; Pneumonia; Respiratory Tract Infections

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cell Physiological Phenomena

Study Design

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

Model Details: Open-label, single-arm study in which all enrolled participants receive nogapendekin alfa-inbakicept (NAI) plus a single IV infusion of allogeneic iNKT cells added to standard of care. Participants receive NAI on Days 1 and 10 and iNKT cells on Day 3; safety review by the SRC after the first 5 participants. Up to 20 participants will be treated and followed for 90 days.

Study Record Dates

• First Submitted: March 13, 2026
• First Posted: March 25, 2026
• Study Start: April 15, 2026
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): January 15, 2027
• Last Updated: May 8, 2026

Record last verified: 2026-05