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

NCT07524257 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: ResQ1010-NSCLC
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

NSCLC (Advanced Non-small Cell Lung Cancer); Metastatic NSCLC

Keywords

non-small cell lung cancer; NSCLC; nogapendekin alfa inbakicept; NAI; ANKTIVA; IL-15 agonist; chemoimmunotherapy; pembrolizumab; platinum chemotherapy; pemetrexed; paclitaxel; nab-paclitaxel; progression-free survival; immunotherapy; molecular profiling

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Overall survival (OS)

  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)

  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

  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)

  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)

  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.

Other Outcomes (6)

• Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  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

  From first dose through 156 weeks (3 years) from first dose or 30 days after last dose, whichever occurs first.

• Changes in Vital Signs

  From first dose through 156 weeks (3 years) from first dose or 30 days after last dose, whichever occurs first.

Study Arms (2)

Experimental: NAI + Pembrolizumab + Chemotherapy

EXPERIMENTAL

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); Drug: Pembrolizumab; Drug: Cisplatin or Carboplatin; Drug: Nab-paclitaxel (squamous) OR Pemetrexed (nonsquamous)

Active Comparator: Pembrolizumab + Chemotherapy

ACTIVE COMPARATOR

First-line standard-of-care chemoimmunotherapy per pembrolizumab + platinum doublet regimens, histology-specific.

Drug: Pembrolizumab; Drug: Cisplatin or Carboplatin; Drug: Nab-paclitaxel (squamous) OR Pemetrexed (nonsquamous); Drug: Nab-paclitaxel OR Paclitaxel OR Docetaxel (squamous); Drug: Pemetrexed (nonsquamous)

Interventions

Pembrolizumab DRUG

200 mg IV q3 weeks.

Active Comparator: Pembrolizumab + Chemotherapy; Experimental: NAI + Pembrolizumab + Chemotherapy

Drug: Nogapendekin alfa inbakicept (NAI) DRUG

1.2 mg SC q3 weeks (15 μg/kg SC if ≥100 kg), up to 35 cycles.

Experimental: NAI + Pembrolizumab + Chemotherapy

Cisplatin or Carboplatin DRUG

Cisplatin 75 mg/m² IV q3w OR carboplatin AUC 5-6 IV q3w (per label).

Active Comparator: Pembrolizumab + Chemotherapy; Experimental: NAI + Pembrolizumab + Chemotherapy

Nab-paclitaxel (squamous) OR Pemetrexed (nonsquamous) DRUG

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: Pembrolizumab + Chemotherapy; Experimental: NAI + Pembrolizumab + Chemotherapy

Nab-paclitaxel OR Paclitaxel OR Docetaxel (squamous) DRUG

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.

Active Comparator: Pembrolizumab + Chemotherapy

Pemetrexed (nonsquamous) DRUG

First-line standard-of-care chemoimmunotherapy per pembrolizumab + platinum doublet regimens, histology-specific.

Active Comparator: Pembrolizumab + Chemotherapy

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.
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Cisplatin; Carboplatin; 130-nm albumin-bound paclitaxel; Pemetrexed; Paclitaxel; Docetaxel

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)

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

Study Design

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

Model Details: Participants are randomized 1:1 to two parallel treatment arms (NAI + pembrolizumab + platinum-based chemotherapy vs pembrolizumab + platinum-based chemotherapy alone). Randomization is stratified by tumor histology (squamous vs nonsquamous NSCLC) and PD-L1 tumor proportion score (TPS ≥1% vs \<1%, with "unknown" PD-L1 classified as \<1%). Each participant remains on the assigned arm throughout the study; there is no planned crossover.

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 13, 2026
• Study Start: May 29, 2026
• Primary Completion (Estimated): May 15, 2029
• Study Completion (Estimated): December 30, 2029
• Last Updated: June 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• 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.
• 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.