Nogapendekin Alfa Inbakicept for Advanced Non-Small Cell Lung Cancer

NCT ID: NCT03520686

Last Updated: 2025-10-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1538 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-18
• Study Completion Date: 2026-12-31

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.

Detailed Description

The protocol divides patients into 4 cohorts (A, B, C and D), with varying prior treatments, histology of cancer, PD-L1 expression status to best compare and match appropriate treatments for those subsets of patients. This study is being performed to determine if adding NAI in the first line treatment setting of advanced non-small cell lung cancer has the potential to enhance outcomes across varying treatment backbones.

Conditions

Non Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A (Experimental)

Group Type: EXPERIMENTAL

NAI + Pembrolizumab

Intervention Type: 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)

NAI + Nivolumab + Ipilimumab

Intervention Type: 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 B (Experimental)

Group Type: EXPERIMENTAL

NAI + Pembrolizumab + Carboplatin + Nab-paclitaxel or Paclitaxel

Intervention Type: 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 C (Experimental)

Group Type: EXPERIMENTAL

Cisplatin/carboplatin and pemetrexed plus pembrolizumab.

Intervention Type: 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

Cisplatin/carboplatin and pemetrexed plus atezolizumab.

Intervention Type: 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

Carboplatin and paclitaxel plus atezolizumab and bevacizumab.

Intervention Type: 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

Carboplatin and nab-paclitaxel plus atezolizumab.

Intervention Type: 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 A (Control)

Group Type: ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type: 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 B (Control)

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: 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 C (Control)

Group Type: ACTIVE_COMPARATOR

Cisplatin/carboplatin and pemetrexed plus pembrolizumab.

Intervention Type: 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

Cisplatin/carboplatin and pemetrexed plus atezolizumab.

Intervention Type: 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

Carboplatin and paclitaxel plus atezolizumab and bevacizumab.

Intervention Type: 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

Carboplatin and nab-paclitaxel plus atezolizumab.

Intervention Type: 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 D (Experimental)

Group Type: EXPERIMENTAL

NAI + Nivolumab + Ipilimumab + Carboplatin + Nab-paclitaxel

Intervention Type: 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)

Interventions

NAI + Pembrolizumab

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)

Intervention Type: DRUG

NAI + Nivolumab + Ipilimumab

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

Intervention Type: DRUG

Pembrolizumab

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)

Intervention Type: DRUG

NAI + Pembrolizumab + Carboplatin + Nab-paclitaxel or Paclitaxel

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

Intervention Type: DRUG

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

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)

Intervention Type: DRUG

Cisplatin/carboplatin and pemetrexed plus pembrolizumab.

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

Intervention Type: DRUG

Cisplatin/carboplatin and pemetrexed plus atezolizumab.

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

Intervention Type: DRUG

Carboplatin and paclitaxel plus atezolizumab and bevacizumab.

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

Intervention Type: DRUG

Carboplatin and nab-paclitaxel plus atezolizumab.

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

Intervention Type: DRUG

NAI + Nivolumab + Ipilimumab + Carboplatin + Nab-paclitaxel

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)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years old.

2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.

3. Histologically-confirmed stage 3 or 4 NSCLC disease. Subjects with stage 3 disease must not be candidates for treatment with surgical resection or chemoradiation.

4. 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.

5. For Cohort A only: NSCLC tumors must have PD-L1 expression (i.e. a TPS ≥1%) as determined by an FDA-approved test.

6. 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.

7. ECOG performance status of 0 or 1.

8. Measurable tumor lesions according to RECIST 1.1.

9. 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.

10. Must be willing to provide blood samples prior to the start of treatment on this study for exploratory tumor molecular profiling analysis.

11. 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.

12. Ability to attend required study visits and return for adequate follow-up, as required by this protocol

13. 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.

1. Age ≥ 18 years old.

2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines

3. Histologically-confirmed stage III or IV NSCLC disease. Participants with stage III disease must not be candidates for treatment with surgical resection or definitive chemoradiation.

4. ECOG performance status of 0 to 2.

5. Measurable tumor lesions according to RECIST v1.1.

6. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.

7. Agreement to practice effective contraception for female participants of childbearing potential and non-sterile males. Female participants of childbearing potential must agree to use effective contraception for up to 7 months after completion of therapy, and nonsterile male participants must agree to use a condom for up to 7 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), orals, injectables. two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and hormonal therapy.

Exclusion Criteria

1. 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.

2. 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.

3. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma).

4. 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.

5. Prior systemic chemotherapy, major surgery, or thoracic radiation within 3 weeks of study initiation.

6. Requirement for other forms of anticancer treatment while on trial, including maintenance therapy, other radiation therapy, and/or surgery. Palliative radiation is permitted.

7. 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.

8. History of receiving a live vaccine 30 days prior to study treatment.

9. History of human immunodeficiency virus (HIV), or known active hepatitis B or C infection.

10. An active infection requiring systemic IV therapy.

11. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

12. Inadequate organ function, evidenced by the following laboratory results:

1. Absolute neutrophil count < 1,500 cells/mm3.

2. Platelet count < 100,000 cells/mm3.

3. Total bilirubin greater the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).

4. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 1.5 × ULN.

5. Alkaline phosphatase (ALP) levels > 2.5 × ULN.

6. Serum creatinine > 2.0 mg/dL or 177 μmol/L or creatinine clearance < 40 mL/min (using the Cockcroft-Gault formula)

13. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication. Subjects with uncontrolled hypertension should be medically managed on a stable regimen to control hypertension prior to study entry.

14. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.

15. Known hypersensitivity to any component of the study medication(s).

16. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.

17. Participation in an investigational drug study or history of receiving any investigational treatment within 30 days prior to screening for this study, except for testosterone-lowering therapy in men with prostate cancer.

18. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.

19. Concurrent participation in any interventional clinical trial.

20. Pregnant and nursing women.

1. Prior systemic therapy or radiation therapy for treatment of current advanced or metastatic NSCLC.

2. Have known EGFR mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 [L858R] substitution mutations). All participants with nonsquamous histology must have been tested for EGFR mutation status; use of an approved test is strongly encouraged. Participants with nonsquamous histology and unknown or indeterminate EGFR status are excluded.

3. Have known ALK translocations which are sensitive to available targeted inhibitor therapy are excluded. If tested, use of an approved test is strongly encouraged.

Participants with unknown or indeterminate ALK status may be enrolled.

4. Systemic autoimmune disease currently requiring treatment (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma). Participants must have been off treatment for 180 days.

5. 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.

6. Requirement for other forms of anticancer treatment while on trial, including maintenance therapy, radiation therapy, and/or surgery. Palliative radiation is permitted.

7. Participants with untreated CNS metastases and carcinomatous meningitis are excluded.

Participants are eligible if CNS metastases are adequately treated and participants are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first treatment. In addition, participants must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone.

8. Active infection requiring systemic IV therapy.

9. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

10. Inadequate organ function, evidenced by the following laboratory results:

1. Absolute lymphocyte count < institutional ULN.

2. Absolute neutrophil count < 1,500 cells/mm3.

3. Platelet count < 100,000 cells/mm3.

4. Total bilirubin greater than the upper limit of normal (ULN; unless the participant has documented Gilbert's syndrome).

5. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 1.5 × ULN.

6. ALP levels > 2.5 × ULN.

7. Hemoglobin < 9.0 g/dL.

8. Serum creatinine > 2.0 mg/dL or 177 μmol/L or creatinine clearance < 40 mL/min (using the Cockcroft-Gault formula below). Female = [(140 - age in years) × weight in kg x 0.85] / [72 × serum creatinine in mg/dL] Male = [(140 - age in years) × weight in kg × 1.00] / [72 × serum creatinine in mg/dL].

11. Participants taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.

12. Participation in an investigational drug study or history of receiving any investigational treatment within 30 days prior to the start of treatment on this study, except for hormone-lowering therapy in participants with hormone-sensitive cancer.

13. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.

14. Pregnant and nursing women.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ImmunityBio, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jayson Garmizo

Role: STUDY_DIRECTOR

Associate Director, Clinical Operations

Locations

Alaska Urological Institute - Alaska Clinical Research Center

Anchorage, Alaska, United States

Genesis Cancer Center

Hot Springs, Arkansas, United States

Chan Soon-Shiong Institute for Medicine

El Segundo, California, United States

Adventist Health Glendale

Glendale, California, United States

MemorialCare Health System

Long Beach, California, United States

Adventist Health White Memorial

Los Angeles, California, United States

Hoag Memorial Hospital

Newport Beach, California, United States

Desert Hematology Oncology Medical Group

Rancho Mirage, California, United States

Memorial Healthcare

Hollywood, Florida, United States

Baptist Health South Florida - Miami Cancer Institute

Miami, Florida, United States

Healthcare Research Network

Tinley Park, Illinois, United States

Baptist Health - Lexington

Lexington, Kentucky, United States

Baptist Health Louisville

Louisville, Kentucky, United States

Karmanos Cancer Center

Detroit, Michigan, United States

Mercy Research Joplin

Joplin, Missouri, United States

St. Vincent Frontier Cancer Center

Billings, Montana, United States

Astera Cancer Care

East Brunswick, New Jersey, United States

University of Rochester

Rochester, New York, United States

Stony Brooke Medicine

Stony Brook, New York, United States

Mercy Research Oklahoma City

Oklahoma City, Oklahoma, United States

LeHigh Valley

Allentown, Pennsylvania, United States

Gettysburg Cancer Center

Gettysburg, Pennsylvania, United States

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

Charleston, South Carolina, United States

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

Greenville, South Carolina, United States

Avera Cancer Institute

Sioux Falls, South Dakota, United States

University of Tennessee Medical Center

Knoxville, Tennessee, United States

Baptist Cancer Center

Memphis, Tennessee, United States

Texas Oncology-Austin

Austin, Texas, United States

Texas Oncology-Bedford

Bedford, Texas, United States

Oncology Consultants, PA

Houston, Texas, United States

Bon Secours Richmond

Richmond, Virginia, United States

Countries

United States

Other Identifiers

QUILT-2.023

Identifier Type: -

Identifier Source: org_study_id