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

Eligibility Criteria: Women and men of all races and ethnic groups are eligible for this trial. Cohort A Inclusion Criteria: 1. Age ≥ 18 years old. 2. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. 3. Pathologically confirmed stage IV NSCLC disease. 4. 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. 5. 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. 6. 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: 1. Participants who have tumors with EGFR L858R or exon 19 deletion mutations must have received prior osimertinib. 2. 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. 3. 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. 4. Participants must also meet the inclusion criteria #4 listed above. 7. ECOG performance status of 0 to 2. 8. Measurable tumor lesions according to RECIST v1.1. 9. Have a life expectancy of at least 3 months. 10. Ability to attend required study visits and return for adequate follow-up, as required by this protocol. 11. 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. 12. 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. Exclusion Criteria: 1. 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. 2. 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. 3. 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. 4. Participants with AGA of ALK. 5. 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.) 6. Active infection requiring antibiotic therapy. 7. Have known active central nervous system (CNS) metastases, carcinomatous meningitis, and/or spinal cord compression. 8. Body weight ≤ 40 kg at screening. 9. Active treatment with CYP3A4 inhibitors. 10. Received a live vaccine ≤ 4 weeks prior to the first dose of study drug(s). 11. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis). 12. Participants with known history of severe hypersensitive reactions to docetaxel or to other drugs formulated with polysorbate 80. 13. 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. 14. Inadequate organ function, evidenced by the following laboratory results: 1. Absolute lymphocyte count \< institutional lower limit of normal (LLN) (ie, participant should have a normal lymphocyte count to enroll in the study). 2. Absolute neutrophil count ≤ 1,500 cells/mm3. 3. Platelet count ≤ 100,000 cells/mm3. 4. 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. 5. Aspartate aminotransferase (AST \[serum glutamic-oxaloacetic transaminase; SGOT\]) or alanine aminotransferase (ALT \[serum glutamic pyruvic transaminase; SGPT\]) \> 1.5 × ULN. 6. Alkaline phosphatase (ALP) levels \> 2.5 × ULN. 7. Hemoglobin \< 9.0 g/dL. 8. 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 = \[(140 - age in years) × weight in kg × 1.00\] / \[72 × serum creatinine in mg/dL\] 15. Have any of following: 1. Cirrhosis at a level of Child-Pugh B (or worse); 2. Cirrhosis (any degree) and a history of hepatic encephalopathy; or 3. Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis. 16. Participation in an investigational drug study within 21 days prior to the start of treatment on this study, except for hormone lowering therapy in participants with hormone-sensitive cancer. Participating in any other interventional clinical trial during active participation in this clinical trial is not allowed. 17. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol. 18. Pregnant and nursing women. 19. History of allergic reactions to tislelizumab. 20. History of prior adverse reaction to immunotherapy that led to its permanent discontinuation. 21. Confinement in an institution by order of a court or authority. Cohort B Inclusion Criteria: 1. Age ≥ 18 years old. 2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines. 3. Pathologically confirmed stage IV NSCLC disease. 4. 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. 5. Participants who receive an immune CPI as consolidation therapy after chemoradiation are eligible if they show progression or recurrence within 3 months of their last CPI and must have received at least 6 months of exactly 1 line of prior CPI therapy. If that CPI is not approved for advanced NSCLC, then an approved alternative CPI will be used. 6. If participants are positive for actionable genomic alteration (AGA), defined as a genomic alteration which has at least 1 regional Health Authority-approved targeted therapy. Participants MUST have received at least 1 targeted therapy or 2 or more if multiple lines of targeted therapies are approved in the region. Thus, participants must have exhausted regional Health Authority-approved targeted therapies for their specific AGA for first- or second-line NSCLC, then have acquired resistance to immune checkpoint therapy to be eligible. Participants must meet inclusion criteria #4. 7. Participants with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks and have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication. Stable brain metastases by this definition should be established prior to the first dose of study medication. Participants with asymptomatic brain metastases (ie, no neurological symptoms, no requirements for corticosteroids, and no lesion \>1.5 cm) may participate but will require regular imaging of the brain as a site of disease. 8. ECOG performance status of 0 to 2. 9. Measurable tumor lesion(s) according to RECIST v1.1. 10. Have a life expectancy of at least 3 months. 11. Ability to attend required study visits and return for adequate follow-up, as required by this protocol. 12. 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. 13. Participants with known HIV infection must be receiving antiretroviral therapy and have an undetectable viral load at their most recent viral load test within 6 months prior to enrollment. Exclusion Criteria: 1. Autoimmune disease currently requiring systemic treatment (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma) except for autoimmune thyroiditis needing thyroid replacement and diabetes requiring insulin. The participant must have been off treatment for 60 days. 2. 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. 3. History of allogeneic hematopoietic stem cell transplant or organ transplant requiring immunosuppression; or history of pneumonitis or interstitial lung disease requiring active treatment with systemic steroids or other systemic therapy; 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. 4. Have an active or uncontrolled hepatitis B and/or hepatitis C infection and are positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (hepatitis B surface antigen \[HBsAg\], anti-hepatitis B surface antibody \[anti-HBs\], anti-hepatitis B core antibody \[anti-HBc\], or hepatitis B virus \[HBV\] DNA), and/or hepatitis C infection (as per hepatitis C virus \[HCV\] RNA) within 28 days of randomization. Participants are eligible if they: 1. Have received hepatitis B vaccination with only anti-HBs positivity and no clinical signs of hepatitis. 2. Have HbsAg+ with HBV infection for more than 6 months (ie, chronic HBV infection) meeting the following conditions: i. HBV DNA viral load \< 2,000 IU/mL. ii. Have normal transaminase values, or, if liver metastases are present, abnormal transaminases with a result of AST/ALT \< 3 ULN that are not attributable to HBV infection. iii. Start or maintain antiviral treatment if clinically indicated as per the Investigator. c. Have been curatively treated for hepatitis. 5. Active infection requiring systemic antibiotic therapy (antiviral therapy is allowed). 6. Have known active central nervous system (CNS) metastases, carcinomatous meningitis, and/or spinal cord compression. 7. Body weight ≤ 40 kg at screening. 8. Received a live vaccine ≤ 4 weeks prior to the first dose of study drug(s). 9. Known history of severe hypersensitive reactions to docetaxel or to other drugs formulated with polysorbate 80. 10. Had major surgery, myocardial infarction, and/or cerebrovascular accident within 28 days prior to study randomization. Participants must have fully recovered from the effects of prior surgery or illness in the opinion of the treating Investigator. 11. Inadequate organ function, evidenced by the following laboratory results: 1. Absolute lymphocyte count \< institutional LLN (ie, participant should have a normal lymphocyte count to enroll in the study). 2. Absolute neutrophil count ≤ 1,500 cells/mm3. 3. Platelet count ≤100,000 cells/mm3. 4. Total bilirubin \> 1.5 times the ULN, unless the participant has documented Gilbert's syndrome). Participants with documented Gilbert's syndrome are to be excluded if total bilirubin is ≥ 3 × ULN or direct bilirubin is \> ULN. 5. Aspartate aminotransferase (AST \[serum glutamic-oxaloacetic transaminase; SGOT\]) or alanine aminotransferase (ALT \[serum glutamic pyruvic transaminase; SGPT\]) \> 1.5 × ULN or \> 5 times ULN for participants with liver metastases. 6. Alkaline phosphatase (ALP) levels \> 2.5 × ULN, \> 5 times ULN for participants with known bone metastases. 7. Hemoglobin \< 9.0 g/dL. 8. 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 = \[(140 - age in years) × weight in kg × 1.00\] / \[72 × serum creatinine in mg/dL\] 12. Have any of the following: 1. Cirrhosis at a level of Child-Pugh B (or worse); 2. Cirrhosis (any degree) and a history of hepatic encephalopathy; or 3. Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis. 13. Participation in an investigational drug study within 28 days prior to the start of treatment on this study, except for hormone lowering therapy in participants with hormone-sensitive cancer. Participating in any other interventional clinical trial during active participation in this clinical trial is not allowed. 14. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol. 15. Pregnant and nursing women. 16. History of prior adverse reaction to immunotherapy that led to its permanent discontinuation. 17. Have a history of malignancy other than NSCLC, except: 1. Adequately resected non-melanoma skin cancer; or, 2. Curatively treated in situ disease or 3. Other curatively treated solid tumors, with no evidence of disease for ≥ 3 years; or 4. Hormone sensitive cancers treated only with hormone therapy. 18. Other antineoplastic therapies intended to treat cancer, including herbal medicines or other prohibited concurrent medication(s) within 28 days prior to the start of treatment in the study. 19. Confinement in an institution by order of a court or authority.