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

NCT07355205 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-X396
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single center, one cohort, non-randomized, phase II study. The aim of the study is to evaluate the efficacy and safety of the combination of nivolumab and ipilimumab with nogapendekin alfa inbakicept in patients with stage IV or recurrent non-small cell lung cancer (NSCLC). It is hypothesized that the study treatment will be safe and well tolerated and will improve progression-free survival when compared to a historical study which treated advanced NSCLC patients with nivolumab plus ipilimumab. Patients will be treated in cycles lasting 6 weeks with two to three different chemotherapy drugs to up to 24 months.

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 (1)

• Progression-free survival (PFS)

  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)

Secondary Outcomes (7)

• Adverse event effect rate

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

• Disease control rate (DCR)

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

• Duration of response (DoR)

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

• Objective response rate (ORR)

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

• Immune-related best overall response (iBOR)

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

Study Arms (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 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

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

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

Nogapendekin alfa inbakicept DRUG

Nogapendekin alfa inbakicept will be given subcutaneously at a dose of 15 μg/kg.

Also known as: N-803, Anktiva

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 EGFR mutation, HER2 mutation, ALK fusion, ROS1 fusion or RET fusion.
• 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:
• History of interstitial lung disease or noninfectious pneumonitis,
• Active viral, bacterial or fungal infections requiring parenteral treatment within 14 days of C1D1,
• Clinically significant cardiovascular disease,
• A condition that may obscure the interpretation of toxicity determination or AEs,
• History of prior solid-organ transplantation.
• Concurrent medical condition requiring the use of supra-physiologic doses of corticosteroids (\> 10 mg/day of oral prednisone or equivalent) or immunosuppressive medications (absorbable topical corticosteroids are not excluded).
• HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
• Evidence of chronic hepatitis B (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.

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

Location

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

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

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)