Phase 3 Study of Nogapendekin Alfa Inbakicept Plus Standard of Care vs Standard of Care in First-Line Advanced or Metastatic NSCLC

Phase 3, Randomized, Open-Label Study of Nogapendekin Alfa Inbakicept in Combination With Standard of Care Versus Standard of Care as First-Line Treatment for Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

This is a randomized, open-label, phase 3 study evaluating nogapendekin alfa inbakicept (NAI) plus chemoimmunotherapy containing pembrolizumab and platinum-based chemotherapy versus chemoimmunotherapy alone as first-line treatment in patients with stage IV squamous or nonsquamous non-small cell lung cancer (NSCLC) without actionable genomic alterations. Primary endpoint is progression-free survival by RECIST v1.1 based on blinded independent central review.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic NSCLC; NSCLC (Advanced Non-small Cell Lung Cancer)
• Intervention / Treatment: Drug: Drug: Nogapendekin alfa inbakicept (NAI); Drug: Pembrolizumab; Drug: Cisplatin or Carboplatin; Drug: Nab-paclitaxel (squamous) OR Pemetrexed (nonsquamous); Drug: Nab-paclitaxel OR Paclitaxel OR Docetaxel (squamous); Drug: Pemetrexed (nonsquamous)

Detailed Description

This is a phase 3, randomized, open-label, parallel-group clinical trial evaluating nogapendekin alfa inbakicept (NAI; an IL-15 receptor agonist) in combination with standard first-line chemoimmunotherapy versus standard chemoimmunotherapy alone in participants with stage IV squamous or nonsquamous non-small cell lung cancer (NSCLC) without actionable genomic alterations that have approved targeted therapies. Approximately 494 participants will be randomized 1:1 to receive either NAI plus pembrolizumab and platinum-based chemotherapy (experimental arm) or pembrolizumab and platinum-based chemotherapy alone (control arm), with the possibility of increasing the sample size up to 960 participants based on an interim progression-free survival (PFS) analysis.

In the experimental arm, participants receive induction therapy for up to 4 cycles (21-day cycles) with pembrolizumab 200 mg IV plus cisplatin 75 mg/m² IV or carboplatin AUC 5-6 IV, and a histology-specific third agent (nab-paclitaxel 100 mg/m² IV on Days 1, 8, and 15 for squamous NSCLC, or pemetrexed 500 mg/m² IV on Day 1 for nonsquamous NSCLC), in combination with NAI 1.2 mg subcutaneously (SC) on Day 1 of each cycle (participants ≥100 kg receive NAI 15 μg/kg SC). In the maintenance phase (cycles ≥5), participants in the experimental arm continue pembrolizumab 200 mg IV every 3 weeks with NAI 1.2 mg SC every 3 weeks, with pemetrexed 500 mg/m² IV continued in nonsquamous NSCLC. In the control arm, participants receive the same pembrolizumab plus platinum backbone, with squamous participants receiving either nab-paclitaxel, paclitaxel, or docetaxel per regional product labeling, and nonsquamous participants receiving pemetrexed, followed by maintenance pembrolizumab with or without pemetrexed according to histology. All study treatment is administered for up to 35 cycles (approximately 2 years), or until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision.

Tumor assessments (CT or MRI) are performed at screening, at week 6 and week 12 following Cycle 1 Day 1, and every 9 weeks (±7 days) thereafter, and tumor response is evaluated per RECIST v1.1 and immune RECIST (iRECIST). The primary endpoint is PFS per RECIST v1.1 as assessed by blinded independent central review (BICR). Key secondary endpoints include overall survival (OS) and objective response rate (ORR) per RECIST v1.1 by BICR. Other secondary endpoints include PFS, ORR, duration of response (DOR), and disease control rate (DCR) by iRECIST (BICR) and by Investigator assessment, change in absolute lymphocyte count (ALC) over time, duration of immune competence (ALC ≥1,000 cells/µL), disease-specific survival (DSS), and safety (treatment-emergent adverse events, serious adverse events, laboratory parameters, vital signs, and ECGs). The study also includes exploratory analyses of whole slide images and blood/tissue-based molecular profiling to explore correlations with clinical outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 494
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tamra Madenwald; Phone Number: 206-512-6881; Email: tamra.madenwald@immunitybio.com
• Study Contact Backup: Name: Joseph Ward; Phone Number: 13236933913; Email: joseph.ward@immunitybio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years.
• Pathologically confirmed stage IV NSCLC (squamous or nonsquamous).
• No prior systemic chemotherapy for advanced/metastatic NSCLC.
• Tumor lacks an actionable genomic alteration with approved first-line targeted therapy (EGFR, ALK etc.; AGA status from local or central testing; ctDNA acceptable if tissue unavailable).
• PD L1 result available before randomization: TPS ≥1%, <1%, or unknown.
• ECOG performance status 0-1.
• At least one measurable lesion per RECIST v1.1.
• Able to attend visits and follow-up.
• Contraception requirements for women of childbearing potential and nonsterile males, with 7 month post-last-dose window.

Exclusion Criteria:

• Body weight <40 kg.
• Serious uncontrolled concomitant disease.
• Certain prior malignancies (exceptions: adequately treated or nonmetastatic, as per protocol).
• Active autoimmune disease requiring systemic treatment (exceptions: autoimmune thyroiditis, etc.).
• Prior organ transplant requiring immunosuppression.
• Prior pneumonitis/interstitial lung disease requiring active systemic treatment.
• Prior systemic chemotherapy or immunotherapy within 3 years.
• Requirement for other anticancer therapy while on study (palliative RT allowed).
• Known CNS metastases, carcinomatous meningitis, and/or spinal cord compression (with specified exceptions for treated or asymptomatic brain mets).
• HIV infection or active/uncontrolled HBV/HCV not meeting the protocol's controlled criteria.
• Active infection requiring IV therapy.
• Inadequate organ function:
• ANC <1,500/mm³; platelets <100,000/mm³; Hgb <9 g/dL.
• Total bilirubin >1.5×ULN (with defined Gilbert's exception).
• AST/ALT >1.5×ULN (or >5×ULN with liver mets).
• ALP >2.5×ULN (or >5×ULN with bone mets).
• Creatinine clearance <40 mL/min (Cockcroft-Gault).
• Significant cardiovascular disease (uncontrolled HTN, recent MI, stroke, CHF ≥NYHA II, serious arrhythmia).
• Known hypersensitivity to study drugs.
• Concomitant medications known to interact adversely with study drugs.
• Participation in another investigational drug/device study (except hormone-lowering therapy).
• Pregnancy or breastfeeding.
• Confinement by court order/authority.
• Any condition or noncompliance that, in Investigator judgment, precludes participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: NAI + Pembrolizumab + Chemotherapy; First-line stage IV NSCLC; induction (≤4 cycles) with pembrolizumab + platinum + nab-paclitaxel (squamous) or pemetrexed (nonsquamous) plus NAI, followed by maintenance pembrolizumab ± pemetrexed plus NAI.	Drug: Drug: Nogapendekin alfa inbakicept (NAI); 1.2 mg SC q3 weeks (15 μg/kg SC if ≥100 kg), up to 35 cycles.; Drug: Pembrolizumab; 200 mg IV q3 weeks.; Drug: Cisplatin or Carboplatin; Cisplatin 75 mg/m² IV q3w OR carboplatin AUC 5-6 IV q3w (per label).; Drug: Nab-paclitaxel (squamous) OR Pemetrexed (nonsquamous); Squamous: nab-paclitaxel 100 mg/m² IV on Days 1, 8, 15 of cycles 1-4. Nonsquamous: pemetrexed 500 mg/m² IV Day 1 q3w, up to 35 cycles.
Active Comparator: Active Comparator: Pembrolizumab + Chemotherapy; First-line standard-of-care chemoimmunotherapy per pembrolizumab + platinum doublet regimens, histology-specific.	Drug: Pembrolizumab; 200 mg IV q3 weeks.; Drug: Cisplatin or Carboplatin; Cisplatin 75 mg/m² IV q3w OR carboplatin AUC 5-6 IV q3w (per label).; Drug: Nab-paclitaxel (squamous) OR Pemetrexed (nonsquamous); Squamous: nab-paclitaxel 100 mg/m² IV on Days 1, 8, 15 of cycles 1-4. Nonsquamous: pemetrexed 500 mg/m² IV Day 1 q3w, up to 35 cycles.; Drug: Nab-paclitaxel OR Paclitaxel OR Docetaxel (squamous); Nab-paclitaxel 100 mg/m² IV D1, 8, 15 or paclitaxel 175 mg/m² IV D1 or docetaxel 75 mg/m² IV D1 (per RHA label/local guidelines) for cycles 1-4 in squamous participants.; Drug: Pemetrexed (nonsquamous); First-line standard-of-care chemoimmunotherapy per pembrolizumab + platinum doublet regimens, histology-specific.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) by BICR (RECIST v1.1)	PFS is defined as the time from randomization to the first documentation of disease progression per RECIST v1.1 by blinded independent central review (BICR) or death from any cause, whichever occurs first.	Imaging every 9 weeks (±7 days) from first dose (after initial assessments at week 6 and week 12) until treatment discontinuation; final PFS analysis with follow-up through 156 weeks (3 years) from first dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Time from randomization to death from any cause.	From first dose until death, with survival follow-up through 156 weeks (3 years) from first dose.
Objective Response Rate (ORR) by BICR (RECIST v1.1)	ORR is the proportion of participants with a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 by BICR.	Imaging every 9 weeks (±7 days) from first dose (after initial assessments at week 6 and week 12) until treatment discontinuation; ORR assessed up to 156 weeks (3 years) from first dose.
Change in Absolute Lymphocyte Count (ALC) Over Time	Change from baseline in absolute lymphocyte count over time by treatment group.	At scheduled study visits from first dose through 156 weeks (3 years) from first dose or end of treatment, whichever occurs first.
Duration of Immune Competence (ALC ≥1,000 cells/µL)	Duration of immune competence, defined as the time during treatment that ALC remains ≥1,000 cells/µL.	From first dose until treatment discontinuation; duration of immune competence assessed up to 156 weeks (3 years) from first dose.
Duration of Response (DOR) by BICR (RECIST v1.1)	For participants with a confirmed CR or PR per RECIST v1.1 by BICR, DOR is defined as the time from the date of first documented response (CR or PR) to the date of disease progression per RECIST v1.1 by BICR or death from any cause, whichever occurs first.	Tumor imaging at week 6 and week 12 following Cycle 1 Day 1, then every 9 weeks (±7 days) from first dose until treatment discontinuation; DOR assessed up to 156 weeks (3 years) from first dose.
Disease Control Rate (DCR) by BICR (RECIST v1.1)	DCR is the proportion of participants with CR, PR, or stable disease (SD) lasting at least 2 months per RECIST v1.1 as assessed by BICR.	Tumor imaging at week 6 and week 12 following Cycle 1 Day 1, then every 9 weeks (±7 days) from first dose until treatment discontinuation; DCR assessed up to 156 weeks (3 years) from first dose.
PFS, ORR, DOR, and DCR by BICR Using iRECIST	PFS, ORR, DOR, and DCR assessed per immune RECIST (iRECIST) as determined by BICR, using the same definitions as for RECIST v1.1 but applying iRECIST rules.	Tumor imaging at week 6 and week 12 following Cycle 1 Day 1, then every 9 weeks (±7 days) from first dose until treatment discontinuation; each endpoint assessed up to 156 weeks (3 years) from first dose.
PFS, ORR, DOR, and DCR by Investigator Assessment (RECIST v1.1 and iRECIST)	PFS, ORR, DOR, and DCR per RECIST v1.1 and iRECIST as assessed by site Investigators, using the same definitions as for BICR.	Tumor imaging at week 6 and week 12 following Cycle 1 Day 1, then every 9 weeks (±7 days) from first dose until treatment discontinuation; each endpoint assessed up to 156 weeks (3 years) from first dose.
Disease-specific survival (DSS)	DSS is defined as the time from randomization to death due to NSCLC. Deaths from other causes are censored at the date of death.	From first dose until death due to NSCLC, with follow-up through 156 weeks (3 years) from first dose.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Number and proportion of participants with TEAEs and SAEs, graded using NCI CTCAE v6.0.	From signing of informed consent through 30 days after last dose of study drug; SAEs considered related to study treatment may be collected beyond this window, up to 156 weeks (3 years) from first dose for analysis.
Changes in Clinical Laboratory Parameters	Changes from baseline in hematology, chemistry, and urinalysis parameters, including ALC.	From first dose through 156 weeks (3 years) from first dose or 30 days after last dose, whichever occurs first.
Changes in Vital Signs	Changes from baseline in temperature, heart rate, blood pressure, and respiratory rate.	From first dose through 156 weeks (3 years) from first dose or 30 days after last dose, whichever occurs first.
Changes in Electrocardiograms (ECGs)	Incidence of new or worsening clinically relevant ECG abnormalities compared with baseline.	From first dose through 156 weeks (3 years) from first dose or 30 days after last dose, whichever occurs first.
Correlation of Whole Slide Images With Clinical Outcomes	Associations between histopathologic features derived from high-resolution whole slide images and clinical outcomes (PFS, OS, ORR, DOR, DCR).	From first dose through 156 weeks (3 years) from first dose.
Correlation of Molecular Profiles With Clinical Outcomes	Associations between tumor and blood-based molecular profiles (e.g., genomic and RNA analyses) and clinical outcomes (PFS, OS, ORR, DOR, DCR, ALC dynamics).	From first dose through 156 weeks (3 years) from first dose.

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): May 29, 2026
• Primary Completion (Estimated): May 15, 2029
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: April 6, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: immunotherapy; NSCLC; non-small cell lung cancer; paclitaxel; nab-paclitaxel; pembrolizumab; pemetrexed; molecular profiling; progression-free survival; chemoimmunotherapy; platinum chemotherapy; NAI; ANKTIVA; nogapendekin alfa inbakicept; IL-15 agonist
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Platinum Compounds; Docetaxel; Pemetrexed; Carboplatin; Paclitaxel; Cisplatin; pembrolizumab; 130-nm albumin-bound paclitaxel
• Other Study ID Numbers: ResQ1010-NSCLC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified participant-level data to be shared include: unique study ID; demographics and baseline characteristics (age, sex, ECOG, histology, PD-L1, AGA status); treatment assignment and exposure (dates offset, doses, modifications); efficacy outcomes and dates (tumor measurements, RECIST/iRECIST responses, PFS, OS, DOR, DCR); safety data (AEs/SAEs with MedDRA codes, CTCAE grade, relatedness); lab results, vitals/ECGs, concomitant meds; processed biomarker datasets and derived pathology/image features. Raw direct identifiers and physical specimens require separate agreements.

IPD Sharing Time Frame

Start date: Data will be made available within 6 months after primary study results are published and any required regulatory review is complete.

End date: Data access will be provided for 5 years from the start date.

• IPD Sharing Access Criteria: Qualified researchers with approved proposals and ethics approval may access de-identified IPD (participant IDs, demographics, treatment/exposure, efficacy/safety outcomes, labs, processed biomarker and derived imaging data) and supporting documents (protocol, SAP, data dictionary) after signing a data use agreement. Data are provided via a secure controlled-access platform; requests are reviewed by the Sponsor.
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No