In this study circulating tumor DNA (ctDNA) blood testing is used to detect the residual
blood cancer. If residual cancer using this blood test is detected there may be at higher
risk of having the cancer return. The study is going to test whether or not the number of
circulating cancer cells detected in the blood can be reduced by administration durvalumab
after the standard treatment if you are tested positive for the residual cancer.
Primary Objective:
The primary objective of this study is to measure the change in ctDNA from trial enrollment
to after 2 cycles of adjuvant durvalumab in subjects with stage I to III NSCLC who had
positive ctDNA following definitive treatment with surgery or radiation and completion of
adjuvant standard of care chemotherapy. Secondary Objectives
1. To compare disease free survival (DFS)
2. To compare overall survival (OS)
3. To evaluate the frequency and severity of toxicity
4. To evaluate the severity of toxicity
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
