This is a phase 3, open-label, 3-cohort, randomized study to compare the safety and efficacy
of N-803 in combination with the current standard of care (experimental arms) versus standard
of care alone (control arms), as first-line treatment for subjects with stage 3 or 4 advanced
or metastatic NSCLC. Treatment will continue for up to 2 years, or until the patient
experiences confirmed progressive disease or unacceptable toxicity, withdraws consent, or if
the investigator feels that it is no longer in the patient's best interest to continue
treatment. Patients will be followed for disease progression, post-therapies, and survival
through 24 months after the first dose of study drug.
1. Age ≥ 18 years old.
2. Able to understand and provide a signed informed consent that fulfills the relevant
IRB or Independent Ethics Committee (IEC) guidelines.
3. Histologically-confirmed stage 3 or 4 NSCLC disease. Subjects with stage 3 disease
must not be candidates for treatment with surgical resection or chemoradiation.
4. Subjects must not have received prior systemic chemotherapy for advanced or metastatic
NSCLC. Previous neoadjuvant/adjuvant chemotherapy is allowed if completed ≥ 6 months
before diagnosis of metastatic disease. Subject's with newly-diagnosed stage 4 NSCLC
may have previously received systemic chemotherapy for stage 3 NSCLC.
5. For Cohort A only: NSCLC tumors must have PD-L1 expression (i.e. a TPS ≥1%) as
determined by an FDA-approved test.
6. The subject's tumor must not harbor an EGFR sensitizing (activating) mutation or ALK
translocation or targetable genomic aberration in BRAF, ROS1 or NTRK. EGFR sensitizing
mutations are those mutations that are amenable to treatment with tyrosine kinase
inhibitors including erlotinib, gefitinib, or afatinib. Investigators must be able to
produce the source documentation of the EGFR mutation, ALK translocation, and BRAF,
ROS1, and NTRK status. If any of the genomic changes described above are detected,
additional information regarding the mutation status of other molecules is not
required. If unable to test for these molecular changes, formalin fixed paraffin
embedded tumor tissue of any age should be submitted to a central laboratory
designated by the Sponsor for such testing. Subjects will not be randomized until the
EGFR , BRAFT, ROS1, and NTRK mutation status and ALK translocation status is available
in source documentation at the site.
7. ECOG performance status of 0 or 1.
8. Measurable tumor lesions according to RECIST 1.1.
9. Must be willing to release tumor biopsy specimen used for diagnosis of advanced or
metastatic NSCLC (if available) for exploratory tumor molecular profiling. If tumor
biopsy specimen is not available, subjects can still be enrolled.
10. Must be willing to provide blood samples prior to the start of treatment on this study
for exploratory tumor molecular profiling analysis.
11. Must be willing to provide a tumor biopsy specimen 9 weeks after the start of
treatment for exploratory analyses, if considered safe by the Investigator.
12. Ability to attend required study visits and return for adequate follow-up, as required
by this protocol
13. Agreement to practice effective contraception for female subjects of child-bearing
potential and non-sterile males. Female subjects of child-bearing potential must agree
to use effective contraception for up to 1 year after completion of therapy, and
non-sterile male subjects must agree to use a condom for up to 4 months after
treatment. Effective contraception includes surgical sterilization (eg, vasectomy,
tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with
spermicide, intrauterine devices (IUDs), hormonal therapy, and abstinence.
1. Serious uncontrolled concomitant disease that would contraindicate the use of the
investigational drug used in this study or that would put the subject at high risk for
2. A history of prior malignancy with the following exceptions: cancer treated with
curative therapy with no disease recurrence for >3 years, non-metastatic prostate
cancer controlled with hormonal therapy, or under observation; non-metastatic thyroid
cancer; basal or squamous cell carcinoma of the skin, superficial bladder cancer, or
in situ cervical cancer that has undergone successful definitive resection.
3. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's
disease, or autoimmune disease associated with lymphoma).
4. History of 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 corticosteroid use to manage AEs are permitted.
5. Prior systemic chemotherapy, major surgery, or thoracic radiation within 3 weeks of
6. Requirement for other forms of anticancer treatment while on trial, including
maintenance therapy, other radiation therapy, and/or surgery. Palliative radiation is
7. Known CNS metastases or carcinomatous meningitis. Subjects with previously treated,
stable CNS metastases (no evidence of progression for ≥ 4 weeks, and resolution of
neurologic symptoms to baseline state) are permitted in this study.
8. History of receiving a live vaccine 30 days prior to study treatment.
9. History of human immunodeficiency virus (HIV), or known active hepatitis B or C
10. An active infection requiring systemic IV therapy.
11. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative
12. Inadequate organ function, evidenced by the following laboratory results:
1. Absolute neutrophil count < 1,500 cells/mm3.
2. Platelet count < 100,000 cells/mm3.
3. Total bilirubin greater the upper limit of normal (ULN; unless the subject has
documented Gilbert's syndrome).
4. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT])
> 1.5 × ULN.
5. Alkaline phosphatase (ALP) levels > 2.5 × ULN.
6. Serum creatinine > 2.0 mg/dL or 177 μmol/L or creatinine clearance < 40 mL/min
(using the Cockcroft-Gault formula)
13. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or
clinically significant (ie, active) cardiovascular disease, cerebrovascular
accident/stroke, or myocardial infarction within 6 months prior to first study
medication; unstable angina; congestive heart failure of New York Heart Association
grade 2 or higher; or serious cardiac arrhythmia requiring medication. Subjects with
uncontrolled hypertension should be medically managed on a stable regimen to control
hypertension prior to study entry.
14. Dyspnea at rest due to complications of advanced malignancy or other disease requiring
continuous oxygen therapy.
15. Known hypersensitivity to any component of the study medication(s).
16. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug
reaction with any of the study medications.
17. Participation in an investigational drug study or history of receiving any
investigational treatment within 30 days prior to screening for this study, except for
testosterone-lowering therapy in men with prostate cancer.
18. Assessed by the Investigator to be unable or unwilling to comply with the requirements
of the protocol.
19. Concurrent participation in any interventional clinical trial.
20. Pregnant and nursing women.