Nogapendekin Alfa Inbakicept for Advanced Non-Small Cell Lung Cancer

NCT03520686 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: QUILT-2.023
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 31

Brief Summary

This is a phase 3, open-label, 4-cohort study (3 randomized cohorts and 1 single-arm cohort). Participants enrolled in each cohort will be treated as detailed below. Each study cohort will be analyzed separately. Treatment will continue for up to 2 years, or until the patient experiences confirmed progressive disease or unacceptable toxicity, withdraws consent, or if the investigator feels that it is no longer in the patient's best interest to continue treatment. Patients will be followed for disease progression, post-therapies, and survival through 24 months after the first dose of study drug.

Conditions

Non Small Cell Lung Cancer

Keywords

Pembrolizumab; N-803; Non-Small Cell Lung Cancer; Immunotherapy; Carboplatin; Cisplatin; Nab-paclitaxel; Paclitaxel; Pemetrexed; Chemotherapy

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS)

  Defined by RECIST Version 1.1 based on BICR

  24 Months

• Change in absolute lymphocyte count (ALC).

  Change in absolute lymphocyte count (ALC) over time in participants treated with NAI in combination with approved CPI(s)

  Significantly Higher ALC Values Over Time Between Experimental & Control Arms Through 27 Weeks

Secondary Outcomes (9)

• Overall Survival (OS)

  24 Months

• Overall Response Rate (ORR)

  24 Months

• Duration of Response (DOR)

  24 Months

• PFS

  24 Months

• Overall Response Rate (ORR)

  24 Months

Other Outcomes (3)

• Incidence of treatment-emergent AEs and SAEs

  24 Months

• Immunogenicity profile of NAI in combination with immune CPI(s) ( Cohorts A, B, and C)

  24 Months

• Tumor molecular profiles and correlations with subject outcomes (Cohorts A, B, C only).

  9 Weeks

Study Arms (7)

Cohort A (Experimental)

EXPERIMENTAL

Drug: NAI + Pembrolizumab; Drug: NAI + Nivolumab + Ipilimumab

Cohort B (Experimental)

EXPERIMENTAL

Drug: NAI + Pembrolizumab + Carboplatin + Nab-paclitaxel or Paclitaxel

Cohort C (Experimental)

EXPERIMENTAL

Drug: Cisplatin/carboplatin and pemetrexed plus pembrolizumab.; Drug: Cisplatin/carboplatin and pemetrexed plus atezolizumab.; Drug: Carboplatin and paclitaxel plus atezolizumab and bevacizumab.; Drug: Carboplatin and nab-paclitaxel plus atezolizumab.

Cohort A (Control)

ACTIVE COMPARATOR

Drug: Pembrolizumab

Cohort B (Control)

ACTIVE COMPARATOR

Drug: Pembrolizumab + Carboplatin + Nab-paclitaxel or Paclitaxel (Investigator's choice)

Cohort C (Control)

ACTIVE COMPARATOR

Drug: Cisplatin/carboplatin and pemetrexed plus pembrolizumab.; Drug: Cisplatin/carboplatin and pemetrexed plus atezolizumab.; Drug: Carboplatin and paclitaxel plus atezolizumab and bevacizumab.; Drug: Carboplatin and nab-paclitaxel plus atezolizumab.

Cohort D (Experimental)

EXPERIMENTAL

Drug: NAI + Nivolumab + Ipilimumab + Carboplatin + Nab-paclitaxel

Interventions

NAI + Pembrolizumab DRUG

This intervention combines Nogapendekin alfa inbakicept (NAI), an immunostimulatory protein complex, with pembrolizumab, an anti-PD-1 immune checkpoint inhibitor, for the treatment of NSCLC in Cohort A of QUILT-2.023. Nogapendekin Alfa Inbakicept (NAI): A soluble complex consisting of two protein subunits of a human IL-15 variant bound with high affinity to a dimeric human IL-15Ra sushi domain/human IgG1 Fc fusion protein (inbakicept), serving as an immunostimulatory agent. Dose: 15 µg/kg Route of Administration: Subcutaneously (SC) Pembrolizumab: A humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby unleashing T-cell mediated immune responses against cancer cells. Dose: 200 mg Route of Administration: Intravenously (IV)

Cohort A (Experimental)

NAI + Nivolumab + Ipilimumab DRUG

Nogapendekin Alfa Inbakicept (NAI): A soluble complex consisting of two protein subunits of a human IL-15 variant bound with high affinity to a dimeric human IL-15Ra sushi domain/human IgG1 Fc fusion protein (inbakicept), serving as an immunostimulatory agent. Dose: 15 µg/kg Route of Administration: Subcutaneously (SC) Nivolumab: A PD-1 blocking antibody that enhances T-cell activity against cancer cells. Dose: 3 mg/kg Route of Administration: Intravenously (IV) Schedule: Days 1, 15, and 29 every 6 weeks Ipilimumab: A CTLA-4 blocking antibody that promotes T-cell activation and anti-tumor immunity. Dose: 1 mg/kg Route of Administration: Intravenously (IV) Schedule: Day 1 every 6 weeks

Cohort A (Experimental)

Pembrolizumab DRUG

Drug: Pembrolizumab The reference treatment will consist of repeated 3-week cycles for a maximum treatment period of 2 years, in accordance with the following dosing regimen: Day 1, every 3 weeks: • Pembrolizumab (200 mg IV)

Cohort A (Control)

NAI + Pembrolizumab + Carboplatin + Nab-paclitaxel or Paclitaxel DRUG

This intervention combines Nogapendekin alfa inbakicept (NAI), pembrolizumab (an anti-PD-1 immune checkpoint inhibitor), carboplatin (a platinum-based chemotherapy drug), and either nab-paclitaxel or paclitaxel (taxane chemotherapies) for the treatment of squamous NSCLC in Cohort B of the QUILT-2.023 trial. Detailed Components: Nogapendekin Alfa Inbakicept (NAI): An immunostimulatory protein complex. Dose: 15 µg/kg Route of Administration: Subcutaneously (SC) Schedule: Day 1 every 3 weeks Pembrolizumab: A PD-1 blocking antibody. Dose: 200 mg Route of Administration: Intravenously (IV) Schedule: Day 1 every 3 weeks Carboplatin: A platinum-based chemotherapy drug. Dose: AUC 6 IV Route of Administration: Intravenously (IV) Schedule: Day 1 every 3 weeks for 4 cycles only (Induction phase) Nab-paclitaxel or Paclitaxel: Taxane chemotherapy drugs. The investigator chooses which one to use

Cohort B (Experimental)

Pembrolizumab + Carboplatin + Nab-paclitaxel or Paclitaxel (Investigator's choice) DRUG

This intervention combines pembrolizumab, a PD-1 inhibitor, with carboplatin, and either nab-paclitaxel or paclitaxel (investigator's choice), for the treatment of squamous NSCLC in the control arm of the QUILT-2.023 trial for cohort B. Detailed Components: Pembrolizumab: A PD-1 blocking antibody. Dose: 200 mg Route of Administration: Intravenously (IV) Schedule: Day 1, every 3 weeks Carboplatin: Chemotherapy agent. Dose: AUC 6 IV Route of Administration: Intravenously (IV) Schedule: Day 1, every 3 weeks for 4 cycles only (Induction phase) Nab-paclitaxel or Paclitaxel: Chemotherapy agents. The investigator chooses which one to use. Nab-paclitaxel Dose: 100 mg/m² Route of Administration: Intravenously (IV) Schedule: Day 1 and Days 8 and 15, every 3 weeks for 4 cycles (Induction phase) Paclitaxel Dose: 200 mg/m² Route of Administration: Intravenously (IV) Schedule: Day 1, every 3 weeks for 4 cycles (Induction phase)

Cohort B (Control)

Cisplatin/carboplatin and pemetrexed plus pembrolizumab. DRUG

Brief Description: Chemoimmunotherapy regimen to treat nonsquamous NSCLC in the experimental or control groups of Cohort C in the QUILT-2.023 study. Detailed Components: Cisplatin or Carboplatin: Cisplatin Dosing: 75 mg/m2, intravenously Route: Intravenously (IV) Schedule: Day 1 every 3 weeks for 4 cycles (Induction Phase) OR Carboplatin: Dosing at AUC 6 IV, intravenously Route: Intravenously (IV) Schedule: Day 1 every 3 weeks for 4 cycles (Induction Phase) Pemetrexed: Dosing at 500 mg/m2, intravenously Route: Intravenously (IV) Schedule: Day 1 every 3 weeks Pembrolizumab: Dosing at 200 mg Route: Intravenously (IV) Schedule: Day 1 every 3 weeks

Cohort C (Control); Cohort C (Experimental)

Cisplatin/carboplatin and pemetrexed plus atezolizumab. DRUG

This is a chemoimmunotherapy regimen to treat nonsquamous NSCLC in the experimental or control groups of Cohort C in the QUILT-2.023 study Detailed Components: Cisplatin or Carboplatin: Chemotherapy agents, the Investigator's choice between one or the other. Cisplatin Dosing: 75 mg/m2, intravenously Route: Intravenously (IV) Schedule: Day 1 every 3 weeks for 4 cycles (Induction Phase) Carboplatin Dosing at AUC 6 IV Route: Intravenously (IV) Schedule: Day 1 every 3 weeks for 4 cycles (Induction Phase) Pemetrexed: Dosing at 500 mg/m2, intravenously Route: Intravenously (IV) Schedule: Day 1 every 3 weeks Atezolizumab: Dosing at 1200 mg Route: Intravenously (IV) Schedule: Day 1 every 3 weeks

Cohort C (Control); Cohort C (Experimental)

Carboplatin and paclitaxel plus atezolizumab and bevacizumab. DRUG

This regimen combines chemotherapy agents with checkpoint and VEGF inhibitors to treat nonsquamous NSCLC in experimental and control groups of Cohort C in QUILT-2.023 trial. Detailed Components: Carboplatin: Dosing at AUC 6 IV Route: Intravenously (IV) Schedule: Day 1 every 3 weeks for 4 cycles (Induction Phase) Paclitaxel: Dosing at 175 or 200 mg/m², intravenously (Investigator's Choice) Route: Intravenously (IV) Schedule: Day 1 every 3 weeks for 4 cycles (Induction Phase) Atezolizumab: Dosing at 1200 mg, intravenously Route: Intravenously (IV) Schedule: Day 1 every 3 weeks Bevacizumab: Dosing at 15mg/kg Route: Intravenously (IV) Schedule: Day 1 every 3 weeks

Cohort C (Control); Cohort C (Experimental)

Carboplatin and nab-paclitaxel plus atezolizumab. DRUG

This regimen combines chemotherapy agents with a checkpoint inhibitor to treat nonsquamous NSCLC in experimental and control groups of Cohort C in QUILT-2.023 trial. Detailed Components: Carboplatin: Chemotherapy agent. Dosing at AUC 6 IV Route: Intravenously (IV) Schedule: Day 1 every 3 weeks for 4 cycles (Induction Phase) Nab-paclitaxel: Chemotherapy agent. Dosing at 100 mg/m², intravenously Route: Intravenously (IV) Schedule: Days 1, 8, and 15 every 3 weeks for 4 cycles (Induction Phase) Atezolizumab: Immunotherapy drug. Dosing at 1200 mg Route: Intravenously (IV) Schedule: Day 1 every 3 weeks

Cohort C (Control); Cohort C (Experimental)

NAI + Nivolumab + Ipilimumab + Carboplatin + Nab-paclitaxel DRUG

This intervention combines Nogapendekin alfa inbakicept (NAI) with the checkpoint inhibitors nivolumab and ipilimumab, carboplatin (a chemotherapy agent), and nab-paclitaxel, and is being explored in NSCLC patients of Cohort D in the QUILT-2.023 trial. Detailed Components: Nogapendekin alfa inbakicept (NAI): Immunomodulatory agent. Dose: 1.2 mg Route of Administration: Subcutaneously (SC) Schedule: Days 1, 15, and 29 of each 6-week cycle Nivolumab: Checkpoint inhibitor. Dose: 360 mg Route of Administration: Intravenously (IV) Schedule: Days 1 and 22 of each cycle Ipilimumab: Checkpoint inhibitor. Dose: 1 mg/kg Route of Administration: Intravenously (IV) Schedule: Day 1 of each cycle Carboplatin: Chemotherapy agent. Dose: AUC 6 Route of Administration: Intravenously (IV) Schedule: Days 1 and 22 (Cycle 1 only) Nab-paclitaxel: Chemotherapy agent. Dose: 100 mg/m2 Route of Administration: Intravenously (IV) Schedule: Days 1, 8, 15, 22, 29, and 36 (Cycle 1 only)

Cohort D (Experimental)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
• Histologically-confirmed stage 3 or 4 NSCLC disease. Subjects with stage 3 disease must not be candidates for treatment with surgical resection or chemoradiation.
• Subjects must not have received prior systemic chemotherapy for advanced or metastatic NSCLC. Previous neoadjuvant/adjuvant chemotherapy is allowed if completed ≥ 6 months before diagnosis of metastatic disease. Subject's with newly-diagnosed stage 4 NSCLC may have previously received systemic chemotherapy for stage 3 NSCLC.
• For Cohort A only: NSCLC tumors must have PD-L1 expression (i.e. a TPS ≥1%) as determined by an FDA-approved test.
• The subject's tumor must not harbor an EGFR sensitizing (activating) mutation or ALK translocation or targetable genomic aberration in BRAF, ROS1 or NTRK. EGFR sensitizing mutations are those mutations that are amenable to treatment with tyrosine kinase inhibitors including erlotinib, gefitinib, or afatinib. Investigators must be able to produce the source documentation of the EGFR mutation, ALK translocation, and BRAF, ROS1, and NTRK status. If any of the genomic changes described above are detected, additional information regarding the mutation status of other molecules is not required. If unable to test for these molecular changes, formalin fixed paraffin embedded tumor tissue of any age should be submitted to a central laboratory designated by the Sponsor for such testing. Subjects will not be randomized until the EGFR , BRAFT, ROS1, and NTRK mutation status and ALK translocation status is available in source documentation at the site.
• ECOG performance status of 0 or 1.
• Measurable tumor lesions according to RECIST 1.1.
• Must be willing to release tumor biopsy specimen used for diagnosis of advanced or metastatic NSCLC (if available) for exploratory tumor molecular profiling. If tumor biopsy specimen is not available, subjects can still be enrolled.
• Must be willing to provide blood samples prior to the start of treatment on this study for exploratory tumor molecular profiling analysis.
• Must be willing to provide a tumor biopsy specimen 9 weeks after the start of treatment for exploratory analyses, if considered safe by the Investigator.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol
• Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 1 year after completion of therapy, and non-sterile male subjects must agree to use a condom for up to 4 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), hormonal therapy, and abstinence.

You may not qualify if:

• Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the subject at high risk for treatment-related complications.
• A history of prior malignancy with the following exceptions: cancer treated with curative therapy with no disease recurrence for \>3 years, non-metastatic prostate cancer controlled with hormonal therapy, or under observation; non-metastatic thyroid cancer; basal or squamous cell carcinoma of the skin, superficial bladder cancer, or in situ cervical cancer that has undergone successful definitive resection.
• Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma).
• History of organ transplant requiring immunosuppression; or history of pneumonitis or interstitial lung disease requiring treatment with systemic steroids; or a history of receiving systemic steroid therapy or any other immunosuppressive medication ≤ 3 days prior to study initiation. Daily steroid replacement therapy (eg, prednisone or hydrocortisone) and corticosteroid use to manage AEs are permitted.
• Prior systemic chemotherapy, major surgery, or thoracic radiation within 3 weeks of study initiation.
• Requirement for other forms of anticancer treatment while on trial, including maintenance therapy, other radiation therapy, and/or surgery. Palliative radiation is permitted.
• Known CNS metastases or carcinomatous meningitis. Subjects with previously treated, stable CNS metastases (no evidence of progression for ≥ 4 weeks, and resolution of neurologic symptoms to baseline state) are permitted in this study.
• History of receiving a live vaccine 30 days prior to study treatment.
• History of human immunodeficiency virus (HIV), or known active hepatitis B or C infection.
• An active infection requiring systemic IV therapy.
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Inadequate organ function, evidenced by the following laboratory results:
• Absolute neutrophil count \< 1,500 cells/mm3.
• Platelet count \< 100,000 cells/mm3.
• Total bilirubin greater the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (31)

Alaska Urological Institute - Alaska Clinical Research Center

Anchorage, Alaska, 99503, United States

Location

Genesis Cancer Center

Hot Springs, Arkansas, 71913, United States

Location

Chan Soon-Shiong Institute for Medicine

El Segundo, California, 90245, United States

Location

Adventist Health Glendale

Glendale, California, 92106, United States

Location

MemorialCare Health System

Long Beach, California, 90806, United States

Location

Adventist Health White Memorial

Los Angeles, California, 90033, United States

Location

Hoag Memorial Hospital

Newport Beach, California, 92663, United States

Location

Desert Hematology Oncology Medical Group

Rancho Mirage, California, 92270, United States

Location

Memorial Healthcare

Hollywood, Florida, 33021, United States

Location

Baptist Health South Florida - Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Healthcare Research Network

Tinley Park, Illinois, 60487, United States

Location

Baptist Health - Lexington

Lexington, Kentucky, 40503, United States

Location

Baptist Health Louisville

Louisville, Kentucky, 40503, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Mercy Research Joplin

Joplin, Missouri, 64804, United States

Location

St. Vincent Frontier Cancer Center

Billings, Montana, 59102, United States

Location

Astera Cancer Care

East Brunswick, New Jersey, 08816, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Stony Brooke Medicine

Stony Brook, New York, 11794, United States

Location

Mercy Research Oklahoma City

Oklahoma City, Oklahoma, 73120, United States

Location

LeHigh Valley

Allentown, Pennsylvania, 18103, United States

Location

Gettysburg Cancer Center

Gettysburg, Pennsylvania, 17325, United States

Location

Medical University of South Carolina (MUSC) - Hollings Cancer Center (HCC)

Charleston, South Carolina, 29425, United States

Location

Saint Francis Cancer Center/Bon Secours St. Francis Health System

Greenville, South Carolina, 29607, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Baptist Cancer Center

Memphis, Tennessee, 38120, United States

Location

Texas Oncology-Austin

Austin, Texas, 78745, United States

Location

Texas Oncology-Bedford

Bedford, Texas, 76002, United States

Location

Oncology Consultants, PA

Houston, Texas, 77030, United States

Location

Bon Secours Richmond

Richmond, Virginia, 23114, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Nivolumab; Ipilimumab; Carboplatin; 130-nm albumin-bound paclitaxel; Paclitaxel; Cisplatin; Pemetrexed; atezolizumab; Bevacizumab

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; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Jayson Garmizo

  Associate Director, Clinical Operations

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2018
• First Posted: May 11, 2018
• Study Start: May 18, 2018
• Primary Completion: October 13, 2025
• Study Completion: October 13, 2025
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (31)