Nogapendekin Alfa Inbakicept for Advanced Non-Small Cell Lung Cancer

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

Interventions

DRUG

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)

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

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)

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

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)

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

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

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

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

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)

Sponsors & Collaborators

• ImmunityBio, Inc.

  lead INDUSTRY

Principal Investigators

• Jayson Garmizo · Associate Director, Clinical Operations

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-05-18

Primary Completion

2025-10-13

Completion

2025-10-13

FDA Drug

Yes

Countries

• United States

Study Locations