Adjuvant Durvalumab for Early Stage NSCLC Patients With ctDNA Minimal Residual Disease

Inclusion Criteria:

1. Histologically or cytologically documented NSCLC who present with stage I to III) disease (Version 8 of American Joint Committee on Cancer(AJCC) Staging Manual)
2. Must have received primary treatment with surgery or definitive stereotactic body radiation therapy (SBRT), and not have known disease progression.
3. Aged 18 years or older
4. Life expectancy ³ 12 weeks
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Appendix B)
6. Absolute neutrophil count > 1.0 x 109/L (1000/mm3)
7. Platelets > 75 x 109/L (100,000/mm3)
8. Hemoglobin ³ 9.0 g/dL (5.59 mmol/L)

9. Measured creatinine clearance > 40 mL/min, by either 24 hour urine collection or the Cockcroft Gault formula

   Males:

   Mass(kg) x (140-Age) / 72 x serum creatinine (mg/dL)

   Females:

   Mass(kg) x (140-Age) x 0.85 / 72 x serum creatinine (mg/dL)

10. Serum bilirubin £ 1.5 x upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of hemolysis or hepatic pathology) who will be allowed in consultation with their physician.
11. Aspartate Aminotransferase (AST) (SGOT)/Alanine Aminotransferase (ALT) (SGPT) £ 2.5 x institutional upper limit of normal (ULN) unless liver metastases are present, in which case it must be £ 5 x ULN
12. AVENIO ctDNA Surveillance Kit Circulating tumor DNA (ctDNA) test result demonstrating either minimal residual disease (MRD) positivity or negativity. Prospective subjects that have indeterminate or no results are NOT ELIGIBLE, but may re test (all other criteria must be met in window).
13. Ability to understand and the willingness to sign the written IRB approved informed consent document.

Exclusion Criteria:

results are NOT ELIGIBLE, but may re test (all other criteria must be met in window).

13.Ability to understand and the willingness to sign the written IRB approved informed consent document.

Identify exclusion criteria.

1. Involvement in the planning and/or conduct of the study
2. Previous enrollment or randomization in the present study
3. Participation in another clinical study with an investigational product (ie, non standard of care) during the last 4 weeks prior to the first dose of trial treatment
4. Must not be planning to receive additional immunotherapy apart from this protocol
5. Mixed small cell and non small cell lung cancer histology
6. anaplastic lymphoma kinase (ALK) or ROS1 mutations, or has Epidermal Growth Factor Receptor (EGFR) mutations and PD L1 levels < 1%
7. Known progression of disease following definitive surgery or radiation
8. Developed Grade 2 or higher pneumonitis from prior radiation
9. History of another primary malignancy and currently undergoing active treatment (ie, chemotherapy, hormonal therapy, biologics)
10. Current or prior use of immunosuppressive medication within 14 days before enrollment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.

11. Any unresolved toxicity CTCAE > Grade 2 from prior therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.

    • Subjects with Grade ³ 2 neuropathy will be evaluated on a case by case basis after consultation with the Protocol Director / Principal Investigator
    • Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by treatment with durvalumab may be included (ie, hearing loss) only after consultation with the Protocol Director / Principal Investigator.

12. Active or prior documented autoimmune or inflammatory disorders which could limit the subjects ability to receive durvalumab on the study (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis; Graves' disease; rheumatoid arthritis; hypophysitis; uveitis; etc]). The following may be taken in to considerations as exceptions to this criterion:

    1. Vitiligo or alopecia
    2. Hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
    3. Chronic skin condition not requiring systemic therapy
    4. Those without active disease in the last 5 years may be included, but only after consultation with the study physician
    5. Celiac disease controlled by diet alone
13. History of primary immunodeficiency
14. History of organ transplant requiring therapeutic immunosuppression

15. Active infection including but not limited to:

    • Tuberculosis
    • Hepatitis B (HBV )[known positive results for HBV surface antigen (HBsAg) within 2 months prior to enrollment]. EXCEPTION: Subjects with a past or resolved HBV infection, defined as the presence of hepatitis B core antibody (anti HBc) and absence of HBsAg are eligible.
    • Hepatitis C (HCV). EXCEPTION: Subjects positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA
16. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Subjects, if enrolled, should not receive live vaccine while receiving the investigational product (IP), and through 30 days after the last dose of IP.

17. Uncontrolled intercurrent illness, including but not limited to:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Uncontrolled hypertension
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Interstitial lung disease