NCT07492888

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.

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: ImmunityBio, Inc. · Industry
• Sex: All
• Age: 18 Years – 105 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

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

Interventions

Type	Name	Description
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.
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.

Timeline

• Start date: 2026-04-15
• Primary completion: 2026-11-15
• Completion: 2027-01-15
• First posted: 2026-03-25
• Last updated: 2026-03-25

Regulatory

• FDA-regulated drug study