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

Recruiting now · Phase 3

Conditions studied: NSCLC Stage IV

In brief

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).

Key facts

Study ID

NCT06745908

Run by

ImmunityBio, Inc.

People needed

507

Starts

2025-10-01

Expected to finish

2029-01-01

Last updated by the study team

2026-07-27

Who can join

Age: 18 and older, up to 90. Sex: any. Healthy volunteers: not accepted.

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.
• Participants must also meet the inclusion criteria #4 listed above.
• 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).
• Absolute neutrophil count ≤ 1,500 cells/mm3.
• Platelet count ≤ 100,000 cells/mm3.
• Participants with documented Gilbert's syndrome are to be excluded if total bilirubin is ≥ 3 × upper limit of normal (ULN) or direct bilirubin is > ULN.
• Aspartate aminotransferase (AST [serum glutamic-oxaloacetic transaminase; SGOT]) or alanine aminotransferase (ALT [serum glutamic pyruvic transaminase; SGPT]) > 1.5 × ULN.
• Alkaline phosphatase (ALP) levels > 2.5 × ULN.
• Hemoglobin < 9.0 g/dL.
• 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 × 0.85] / [72 × serum creatinine in mg/dL] Male = [(140 - age in years) × weight in kg × 1.00] / [72 × serum creatinine in mg/dL]
• Have any of following:
• Cirrhosis at a level of Child-Pugh B (or worse);

Where it is running

• Betsi Cadwaladr University Health Board Wrexham Maelor Hospital — Wrexham, Wrexham, United Kingdom (enrolling)
• Chan Soon-Shiong Institute for Medicine — El Segundo, California, United States (enrolling)
• MemorialCare - Orange Coast Medical Center — Fountain Valley, California, United States (enrolling)
• University Hospital Birmingham NHS Trust — Birmingham, West Midlands, United Kingdom (enrolling)
• Highlands Oncology Group — Springdale, Arkansas, United States (enrolling)
• Holy Cross Hospital — Fort Lauderdale, Florida, United States (enrolling)
• The Oncology Institute of Hope and Innovation — Fort Lauderdale, Florida, United States (enrolling)
• Moffit Cancer Center — Tampa, Florida, United States (enrolling)
• Emory University - Winship Cancer Institute — Atlanta, Georgia, United States (enrolling)
• Barnes-Jewish Hospital - Siteman Cancer Center (Washington University - St. Louis) — St Louis, Missouri, United States (enrolling)
• Carolina Oncology Specialists — Hickory, North Carolina, United States (enrolling)
• University of Cincinnati Medical Center — Cincinnati, Ohio, United States (enrolling)
• University Hospitals Cleveland Medical Center — Cleveland, Ohio, United States (enrolling)
• Medical University of South Carolina — Charleston, South Carolina, United States (enrolling)
• Tennessee Oncology — Nashville, Tennessee, United States (enrolling)
• Vanderbilt - Ingram Cancer Center — Nashville, Tennessee, United States (enrolling)
• Virginia Cancer Specialists — Fairfax, Virginia, United States (enrolling)
• Virginia Commonwealth University — Richmond, Virginia, United States (enrolling)
• Medical Oncology Associates - Summit Cancer Centers — Spokane, Washington, United States (enrolling)
• Vancouver Coastal Health — North Vancouver, British Columbia, Canada (enrolling)
• Horizon Health Network - Saint John Regional Hospital (SJRH) — Saint John, New Brunswick, Canada (enrolling)
• William Osler Health System - Brampton Civic Hospital — Brampton, Ontario, Canada (enrolling)
• Waterloo Regional Health Network - Midtown — Kitchener, Ontario, Canada (enrolling)
• London Health Sciences Centre - Verspeeten Family Cancer Centre — London, Ontario, Canada (enrolling)
• Southlake Regional Health Centre — Newmarket, Ontario, Canada (enrolling)

Full record on ClinicalTrials.gov

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