Durvalumab for the Treatment of Patients with Stage IA2-III Non-small Cell Lung Cancer who Have Minimal Residual Disease
- Pathologically (histologically or cytologically proven) non-small cell lung cancer (NSCLC). Tumors with any component of small cell lung cancer are not allowed. Must NOT be known positive for EGFR TKI sensitizing mutation (Exon 19 deletion or L858R mutation), or ALK/ ROS1 rearrangement. Exception: EGFR mutant NSCLC with PD-L1 expression of 1% or higher is allowed if not planned to receive adjuvant EGFR TKI).
- American Joint Committee on Cancer (AJCC) 8th edition stage IA2 to III disease. Stage IA1 tumors are excluded - must have radiographic solid component -or- pathologic invasive component of > 10 mm
- Received therapy with surgery or definitive (curative intent) radiation * Note: May have received chemotherapy. Radiotherapy is also allowed for patients who have had surgery
- Completed all intended therapy (surgery, radiation, and/or chemotherapy) – AND- no more than 12 weeks has elapsed after the last day of this therapy
- No known residual disease after intended therapy, for example: * No positive margins after surgery without adjuvant radiotherapy * No disease present radiographically (in the investigator’s assessment of probably likelihood or higher)
- Not received immunotherapy (PD-1, PD-L1, or CTLA-4 antibodies) or be intended to receive immunotherapy, apart from this study
- Not received another systemic anti-cancer investigational product during the 4 weeks prior to enrollment
- Aged 18 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy >= 12 weeks
- Absolute neutrophil count > 1.0 x 10^9/L
- Platelets > 75 x 10^9/L
- Hemoglobin >= 9.0 g/dL
- Measured creatinine clearance > 40 mL/min, by either 24 hour urine collection or the Cockcroft Gault formula
- 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
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN)
- Ability to understand and the willingness to sign the written Institutional Review Board (IRB) approved informed consent document
- Women of childbearing potential or their male partner must agree to use a highly effective method of contraception from enrollment until 8 months after final study therapy
- Involvement in the planning and/or conduct of the study
- Previous enrollment or randomization in the present study
- History of grade 3 or higher pneumonitis from prior radiation; patients with grade 2 radiation pneumonitis may be considered for enrollment with permission from the Protocol Director or Co-Director
- History of another primary malignancy and currently undergoing active treatment (ie, chemotherapy, hormonal therapy, biologics)
- Current or prior use of immunosuppressive medication within 14 days before enrollment. Exceptions: intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
- Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) > grade 2 from prior therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. * Subjects with grade > 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) with permission from the Protocol Director / Co-Director
- Active or prior documented autoimmune or inflammatory disorders which could limit the subject's 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: * Vitiligo or alopecia * Hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement * Chronic skin condition not requiring systemic therapy * Those without active disease in the last 5 years may be included with permission from the Protocol Director / Co-Director * Celiac disease controlled by diet alone
- History of primary immunodeficiency
- History of organ transplant requiring therapeutic immunosuppression
- Active infection including but not limited to: * Known Tuberculosis * Known Hepatitis B (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 * Known Hepatitis C (HCV) EXCEPTION: Subjects positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA) * Known human immunodeficiency virus (HIV) infection
- Receipt of live attenuated vaccine within 30 days prior to enrollment. 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
- Uncontrolled intercurrent illness, including but not limited to: * Ongoing or active grade 3 or higher infection * Symptomatic congestive heart failure * Uncontrolled hypertension * Unstable angina pectoris * Cardiac arrhythmia * Interstitial lung disease * Serious chronic gastrointestinal conditions associated with diarrhea * Psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the subject to give written informed consent
- Female subjects who are pregnant or breast feeding
- Any other medical condition that, in the investigator’s opinion, makes the subject unsuitable for enrollment and study procedures
I. To measure the change between pre and post treatment values for circulating tumor deoxyribonucleic acid (ctDNA) levels in subjects with baseline positive MRD (Cohort 1 MRD positive [+]).
I. To determine the proportion of subjects in whom ctDNA becomes completely undetectable after durvalumab (Cohort 1 MRD+).
II. To describe overall survival (OS) of subjects with detectable and undetectable ctDNA at enrollment (Cohort 1 MRD+ and Cohort 2 MRD negative [-]).
III. To compare disease free survival (DFS) of subjects with detectable and undetectable ctDNA at enrollment (Cohort 1 MRD+ and Cohort 2 MRD-).
IV. To evaluate the frequency and severity of toxicity of adjuvant durvalumab (Cohort 1 MRD+) patients that received at least 1 dose of study treatment).
Patients undergo ctDNA testing. Patients are assigned to 1 of 2 cohorts.
COHORT I (MRD+): Within 2 weeks of MRD+ test result, patients with detectable ctDNA receive durvalumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ctDNA testing on day 1 of cycle 1 and after 2 cycles of durvalumab. Patients unable to complete 2 cycles of durvalumab treatment undergo ctDNA testing at 8 weeks. In the absence of disease progression or toxicity, patients continue to receive durvalumab IV over 60 minutes every 28 days for up to 10 additional cycles.
COHORT II (MRD-): Patients without detectable ctDNA undergo surveillance.
After completion of study treatment, patients are followed up every 3-12 months for up to 5 years.
Trial Phase Phase II
Trial Type Treatment
Stanford Cancer Institute Palo Alto
Joel William Neal
- Primary ID LUN0115
- Secondary IDs NCI-2021-03445
- Clinicaltrials.gov ID NCT04585477