Clinical Trial of N-803 Plus Tislelizumab or Prior Failed Immune Checkpoint Inhibitor and Docetaxel Versus Docetaxel Monotherapy in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Acquired Resistance to Immune Checkpoint In

NCT06745908 | Recruiting Phase 3 FDA Drug

• 1 other identifier: ResQ201A-NSCLC
• Study Type: interventional
• Target: 507
• Locations: 1 country
• Sites: 19

Brief Summary

This is a randomized, two-cohort, open-label, phase 3, clinical trial to compare the efficacy and safety of N-803 plus tislelizumab and docetaxel (cohort A) or prior failed Health Authority-approved antiprogrammed death-1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) CPI and docetaxel (cohort B) versus docetaxel monotherapy (cohorts A and B). For each cohort, enrolled participants will be randomized 2:1 to treatment in the experimental arm or the control arm. For cohort A, the randomization will be stratified by geographical region (North America vs Europe vs Asia vs Other), NSCLC histology (squamous vs nonsquamous), and actionable genomic alteration (AGA) (epidermal growth factor receptor \[EGFR\]/anaplastic lymphoma kinase \[ALK\]/ROS proto-oncogene 1, receptor tyrosine kinase \[ROS1\] vs Other AGA vs No AGA). For cohort B, the randomization will be stratified by geographical region (Americas vs Asia Pacific \[PAC\] vs Other), NSCLC histology (squamous vs nonsquamous), and actionable genomic alteration (AGA) (Yes vs No).

Conditions

NSCLC Stage IV

Outcome Measures

Primary Outcomes (1)

• Compare Overall Survival between the experimental and control arms

  Approximately 12 months

Study Arms (4)

Cohort A: Experimental Arm

EXPERIMENTAL

3-week cycles. N803, Tislelizumab, and Docetaxel will be administered on Cycle 1 and 2. N803 and Tislelizumab will be administered on Cycle 3 and onward until end of study.

Drug: N-803; Drug: Tislelizumab; Drug: Docetaxel

Cohort A: Control Arm

ACTIVE COMPARATOR

The control arm treatment regimen will consist of repeated 3-week cycles with a ± 3-day window for each visit of Docetaxel 75 mg/m2 IV.

Drug: Docetaxel

Cohort B: Experimental Arm

EXPERIMENTAL

3-week cycles. N803, prior failed checkpoint inhibitor, and Docetaxel will be administered on Cycle 1 and 2. N803 and prior failed checkpoint inhibitor will be administered on Cycle 3 and onward until end of study.

Drug: N-803; Drug: Docetaxel; Drug: Prior failed checkpoint inhibitor

Cohort B: Control Arm

ACTIVE COMPARATOR

The control arm treatment regimen will consist of repeated 3-week cycles with a ± 3-day window for each visit of Docetaxel 75 mg/m2 IV.

Drug: Docetaxel

Interventions

N-803 DRUG

N-803 1.2 mg SC

Cohort A: Experimental Arm; Cohort B: Experimental Arm

Docetaxel DRUG

Docetaxel 75 mg/m2 IV

Cohort A: Control Arm; Cohort A: Experimental Arm; Cohort B: Control Arm; Cohort B: Experimental Arm

Prior failed checkpoint inhibitor DRUG

Previously failed checkpoint inhibitor

Cohort B: Experimental Arm

Tislelizumab DRUG

Tislelizumab 200 mg IV

Cohort A: Experimental Arm

Eligibility Criteria

• Age: 18 Years - 90 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 Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
• Pathologically confirmed stage IV NSCLC disease.
• Have acquired resistance to a regional Health Authority-approved immune plus platinum-based chemotherapy, defined as disease progression immediately following an initial response (of any duration) or stable disease (approximately 6 months duration \[± 2 weeks\]). Participants who received anti-PD-1/anti-PD-L1 mAb as first-line therapy may have received the combination of platinum-based chemotherapy and anti-PD-1/anti-PD-L1 mAb in the second line. Participants must have received platinum chemotherapy to be eligible. Participants must have received anti-PD-1/anti-PD-L1 mAb in their immediate prior line of therapy to be eligible.
• Participants with AGA must have 1 or more documented AGA(s): EGFR, ROS1, neurotrophic tyrosine receptor kinase (NTRK), B rapidly accelerated fibrosarcoma (BRAF), mesenchymal epithelial transition (MET) exon 14 skipping, rearranged during transfection (RET), Kirsten Rat sarcoma (KRAS) and HER2.
• Participants with AGA must meet the following criteria for advanced or metastatic NSCLC. Participants who have been treated with 1 or 2 prior lines of applicable targeted therapy that is locally approved (and is standard of care) for the participant's genomic alteration at the time of screening:
• Participants who have tumors with EGFR L858R or exon 19 deletion mutations must have received prior osimertinib.
• Participants who received a targeted agent as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose or received at least one additional course of targeted therapy for the same genomic alteration (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease.
• Participants who have been treated with a prior tyrosine kinase inhibitor (TKI) must receive additional approved targeted therapy, if locally available and clinically appropriate, for the applicable genomic alteration, or the participant will not be allowed in the study.
• ECOG performance status of 0 to 2.
• Measurable tumor lesions according to RECIST v1.1.
• Have a life expectancy of at least 3 months.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• Agreement to practice effective contraception for female participants of child-bearing potential and nonsterile males. Female participants of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Female participants of childbearing potential must have a negative serum pregnancy test at screening and adhere to using a highly effective method of contraception (eg, tubal ligation, approved hormonal contraceptive associated with inhibition of ovulation, or an intrauterine device \[IUD\]) prior to screening and agree to continue its use during the study or be surgically sterilized (eg, hysterectomy) while on study and for 7 months post last dose of study drug. Male participants must agree to use barrier methods of birth control while on study and for 7 months post last dose of study drug.
• Participants with known HIV infection must be receiving anti retroviral therapy and have an undetectable viral load at their most recent viral load test within 6 months prior to enrollment.

You may not qualify if:

• Systemic autoimmune disease currently requiring treatment (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma). The participant must have been off treatment for 180 days.
• History of any of the following: drug-induced severe cutaneous adverse reaction (SCAR), including, but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), or dose-limiting immune-mediated reactions.
• History of allogeneic hematopoietic stem cell transplant or 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 corticosteroids used to manage AEs are permitted.
• Participants with AGA of ALK.
• History of known active hepatitis B or C infection to be assessed within 6 months prior to enrollment using locally accepted standard of care measurements. (Resolved cases are allowed.)
• Active infection requiring antibiotic therapy.
• Have known active central nervous system (CNS) metastases, carcinomatous meningitis, and/or spinal cord compression.
• Body weight ≤ 40 kg at screening.
• Active treatment with CYP3A4 inhibitors.
• Received a live vaccine ≤ 4 weeks prior to the first dose of study drug(s).
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Participants with known history of severe hypersensitive reactions to docetaxel or to other drugs formulated with polysorbate 80.
• Had major surgery within 28 days prior to study randomization. Participants must have fully recovered from the effects of prior surgery in the opinion of the treating Investigator.
• Inadequate organ function, evidenced by the following laboratory results:
• Absolute lymphocyte count \< institutional lower limit of normal (LLN) (ie, participant should have a normal lymphocyte count to enroll in the study).

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (19)

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

RECRUITING

Chan Soon-Shiong Institute for Medicine

El Segundo, California, 90245, United States

RECRUITING

MemorialCare - Orange Coast Medical Center

Fountain Valley, California, 92708, United States

RECRUITING

OPN Healthcare INC

Glendale, California, 91203, United States

RECRUITING

OPN Healthcare INC/ Cancer and Blood Specialty Clinic

Los Alamitos, California, 90720, United States

RECRUITING

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

RECRUITING

The Oncology Institute of Hope and Innovation

Fort Lauderdale, Florida, 33316, United States

RECRUITING

Moffit Cancer Center

Tampa, Florida, 33612-9497, United States

RECRUITING

Emory University - Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Barnes-Jewish Hospital - Siteman Cancer Center (Washington University - St. Louis)

St Louis, Missouri, 63110, United States

RECRUITING

Carolina Oncology Specialists

Hickory, North Carolina, 28602, United States

RECRUITING

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

RECRUITING

Medical Oncology Associates - Summit Cancer Centers

Spokane, Washington, 99208, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

ALT-803; tislelizumab; 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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Central Study Contacts

Phillip Trieu

CONTACT

856-739-5609; Phillip.Trieu@immunitybio.com

Tamra Madenwald

CONTACT

Tamra.Madenwald@immunitybio.com

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: December 17, 2024
• First Posted: December 20, 2024
• Study Start: October 1, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: May 5, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)