First-Line Ipilimumab Plus Nivolumab and Nogapendekin Alfa Inbakicept (N-803) in Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer

NCT07355205 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202602160
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, phase Ib/II study combining an anti-PD-1 antibody and an anti-CTLA-4 antibody with IL-15. It is testing the hypothesis that the addition of nogapendekin alfa inbakicept to nivolumab and ipilimumab will augment the clinical activity of those two drugs.

Conditions

Non-small Cell Lung Cancer Recurrent; Non-small Cell Lung Cancer Stage IV

Keywords

Non-small cell lung cancer; Stage IV; Immunotherapy; IL-15 super agnoist

Outcome Measures

Primary Outcomes (2)

• Progression-free survival (PFS) (Phase Ib acceptable dose participants and Phase II participants)

  PFS is defined as the duration of time from the start date of study treatment to the date of earliest progression or death, whichever occurs first. Patients who neither progress nor die by the data cutoff date will be censored at the last follow up date.

  Start of treatment through 2 years after end of treatment (up to 4 years)

• Incidence of dose-limiting toxicities (DLTs) (Phase Ib participants)

  DLTs are defined in the protocol.

  From start of treatment through completion of cycle 1 (each cycle is 42 days)

Secondary Outcomes (7)

• Adverse event effect rate (All participants)

  Start of treatment through 100 days after discontinuation of therapy (up to 2 years and 100 days)

• Disease control rate (DCR) (Phase Ib acceptable dose participants and Phase II participants)

  Start of treatment through 2 years after end of treatment (up to 4 years)

• Duration of response (DoR) (Phase Ib acceptable dose participants and Phase II participants) (Phase Ib acceptable dose participants and Phase II participants)

  Start of treatment through 2 years after end of treatment (up to 4 years)

• Objective response rate (ORR) (Phase Ib acceptable dose participants and Phase II participants)

  Start of treatment through completion of treatment or progression (up to 2 years)

• Immune-related best overall response (iBOR) (Phase Ib acceptable dose participants and Phase II participants)

  Start of study treatment to up to 2 years after the end of treatment (up to 4 years)

Study Arms (3)

Phase Ib Dose Level 1: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803)

EXPERIMENTAL

Consenting and eligible patients will receive nivolumab intravenously (IV) on Days 1 and 22, ipilimumab IV on Day 1, and the assigned dose of nogapendekin alfa inbakicept subcutaneously (SC) on Days 1 and 22 of each cycle for Cycles 1 through 4; ipilimumab will be discontinued after Cycle 4 and patients will continue to receive nivolumab and nogapendekin alfa inbakicept on the same schedule for up to 2 years. Cycles are 42 days (6 weeks).

Drug: Ipilimumab; Drug: Nivolumab; Drug: Nogapendekin alfa inbakicept

Phase Ib Dose Level -1: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803)

EXPERIMENTAL

Consenting and eligible patients will receive nivolumab intravenously (IV) on Days 1 and 22, ipilimumab IV on Day 1, and the assigned dose of nogapendekin alfa inbakicept subcutaneously (SC) on Days 1 and 22 of each cycle for Cycles 1 through 4; ipilimumab will be discontinued after Cycle 4 and patients will continue to receive nivolumab and nogapendekin alfa inbakicept on the same schedule for up to 2 years. Cycles are 42 days (6 weeks).

Drug: Ipilimumab; Drug: Nivolumab; Drug: Nogapendekin alfa inbakicept

Phase II: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803)

EXPERIMENTAL

Consenting and eligible patients will receive nivolumab intravenously (IV) on Days 1 and 22, ipilimumab IV on Day 1, and the assigned dose of nogapendekin alfa inbakicept subcutaneously (SC) on Days 1 and 22 of each cycle for Cycles 1 through 4; ipilimumab will be discontinued after Cycle 4 and patients will continue to receive nivolumab and nogapendekin alfa inbakicept on the same schedule for up to 2 years. Cycles are 42 days (6 weeks).

Drug: Ipilimumab; Drug: Nivolumab; Drug: Nogapendekin alfa inbakicept

Interventions

Ipilimumab DRUG

Ipilimumab will be given intravenously at a dose of 1mg/kg.

Also known as: Yervoy

Phase II: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803); Phase Ib Dose Level -1: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803); Phase Ib Dose Level 1: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803)

Nivolumab DRUG

Nivolumab will be given intravenously at a dose of 360mg.

Also known as: Opdivo

Phase II: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803); Phase Ib Dose Level -1: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803); Phase Ib Dose Level 1: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803)

Nogapendekin alfa inbakicept DRUG

Nogapendekin alfa inbakicept will be given subcutaneously at the assigned dose level.

Also known as: N-803, Anktiva

Phase II: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803); Phase Ib Dose Level -1: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803); Phase Ib Dose Level 1: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed, previously untreated or recurrent metastatic NSCLC.
• Availability of archival biopsy tissue or willingness to undergo a biopsy prior to C1D1 for biomarker analysis, including PD-L1 by IHC using a CLIA-certified test. Results of the PD-L1 testing are not required for enrollment.
• Measurable disease per RECIST 1.1.
• At least 18 years of age.
• ECOG performance status ≤ 1
• Adequate organ and marrow function, as defined below:
• Absolute neutrophil count ≥ 1.5 K/cumm
• Platelets ≥ 100 K/cumm
• Hemoglobin ≥ 9.0 g/dL
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN without hepatic metastasis and ≤ 5 x IULN with hepatic metastasis
• Total bilirubin ≤ 2 x IULN (except participants with Gilbert's syndrome who must have total bilirubin \< 3.0 mg/dL)
• Creatinine clearance \> 30 mL/min by Cockcroft-Gault
• INR ≤ 1.5 unless using therapeutic anticoagulation
• PTT/aPTT \< 1.5 x IULN unless using therapeutic anticoagulation
• Patients with brain metastases are eligible if they have previously treated with surgery or radiation therapy, are neurologically stable after a washout period of at least 2 weeks, and are not receiving corticosteroids at dose higher than 10 mg of prednisone or equivalent on C1D1.

You may not qualify if:

• Mixed histology including small cell lung cancer.
• Tumor harboring any of the following:
• classic EGFR mutations
• HER2 mutation
• ALK fusion
• ROS1 fusion
• RET fusion
• NTRK fusion
• MET Exon14 skipping mutation
• BRAF V600E mutation
• Use of any live vaccines within 28 days of C1D1.
• Prior chemotherapy in the adjuvant setting or during concurrent radiation therapy for locally advanced disease within 12 months prior to enrollment. If the interval from the last treatment is 12 months or longer, the patient is eligible.
• Radiation therapy within 14 days prior to C1D1.
• History of major surgery within 14 days prior to C1D1.
• Underlying medical conditions that, in the Investigator's opinion, will make the administration of study treatment hazardous, including but not limited to:

Sponsors & Collaborators

• ImmunityBio, Inc.: collaborator
• Washington University School of Medicine: lead
• The Foundation for Barnes-Jewish Hospital: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Ipilimumab; Nivolumab; ALT-803

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Giordano Fabricio Cittolin Santos, MD, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giordano Fabricio Cittolin Santos, MD, PhD

CONTACT

314-273-4731; cgiordano@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2026
• First Posted: January 21, 2026
• Study Start: July 7, 2026
• Primary Completion (Estimated): July 31, 2032
• Study Completion (Estimated): July 31, 2032
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)