Evaluation of a Cancer Lysate Vaccine and Montanide (Registered Trademark) ISA-51 VG With or Without the IL-15 Super-Agonist N-803 as Adjuvant Therapy for PD-L1 Negative Non-Small Cell Lung Cancer

INCLUSION CRITERIA:
Participant with histologically or cytologically proven Stage IB-IIIA (T2a-T4/N0, T1- T3N1, T1-T2/N2) NSCLC per 8th edition TNM Staging System with no clinical evidence of active disease (NED) or minimal residual disease (MRD) not readily accessible by non-invasive biopsy or resection/radiation following standard therapy. Initial diagnosis must be confirmed by the NIH Laboratory of Pathology.
History of PD-L1 expression in cancer cells < 1% as determined by IHC analysis.
Participant must be enrolled within 12 weeks following completion of prior SOC therapy.
Participant must have an ECOG performance status of 0-2.
Participant must be >=18 years of age.
Participant must be willing to co-enroll on protocol 06C0014 (Prospective Analysis of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies) allowing for the collection of blood for correlative experiments pertaining to this protocol and related translational research efforts in the Thoracic Surgery Branch.
Participant must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters (all eligibility assessment/enrollment bloodwork must be done at NIH no more than 2 weeks prior to enrollment):
Absolute neutrophil count greater than 1500/mm3
Absolute lymphocyte count greater than 800/mm3
Platelet count greater than 75,000/mm3
Hemoglobin greater than 8 g/dL (participant may receive transfusions to meet this parameter)
INR< 1.5xULN
Total bilirubin < 1.5 x upper limits of normal (except those with Gilberts disease)
Serum creatinine less than or equal to 1.6 mg/mL or the eGFR must be greater than 60 mL/min/1.73m2
Seronegative for HIV antibody by bloodwork performed at NIH no more than 4 weeks prior to enrollment.
Seronegative for active hepatitis B, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RTPCR and be HCV RNA negative by bloodwork performed at NIH no more than 4 weeks

prior to enrollment.

Participants who are breastfeeding or plan to breastfeed must agree to discontinue/postpone breastfeeding while receiving investigational treatment and for 120 days after the last dose of vaccine or N-803.
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) within 28 days prior initiation of study therapy, for the duration of study participation and up to 120 days after the last

dose of the drug.

-Participant must be able to understand and willing to sign an informed consent.

EXCLUSION CRITERIA:

Participants receiving other investigational agents.
Participants on any active treatment for their cancer upon study entry.
Participant who is initially rendered NED or have MRD following standard therapy but exhibit disease progression prior to initiation of vaccination.
Participant requiring chronic systemic treatment with steroids above physiologic doses.
Participant receiving warfarin anticoagulation, who cannot be transitioned to other agents such as enoxaparin or dabigatran, and for whom anticoagulants cannot be held for up to 24 hours.
Participant with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated CHF (> NYHA Class II), or myocardial infarction within 6 months prior to initiation of study therapy.
Participant with any of the following pulmonary function abnormalities: FEV, < 35% predicted; DLCO < 35% predicted (post-bronchodilator); oxygen saturation less than 92% on room air based on assessment at NIH or outside medical facility no more than 4 weeks prior to protocol enrollment.
Active COVID infection
Participant pregnancy
Uncontrolled intercurrent illness occurring within 3 months prior to initiation of study therapy /social situations (as assessed by social services) that would limit compliance with study requirements.