| Eligibility |
Inclusion Criteria:
1. Histologically confirmed operable NSCLC (resectable stage IIA~IIIB) regardless of
PD-L1 expression.
2. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target
lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic
resonance imaging (MRI) must be performed within 28 days prior to neoadjuvant
durvalumab.
3. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol. Written informed consent and any locally required authorization (eg, Health
Insurance Portability and Accountability Act in the US, European Union [EU] Data
Privacy Directive in the EU) obtained from the patient/legal representative prior to
performing any protocol-related procedures, including screening evaluations.
4. Male or female, 18 years or older (at the consent is obtained). Note: In the Republic
of Korea, a participant must be over 19 years of age inclusive, at the time of signing
the informed consent.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Life expectancy of > 12 weeks
7. Body weight >30 kg
8. Adequate normal organ and marrow function as defined below:
Hemoglobin =9.0 g/dL Absolute neutrophil count (ANC) =1.0 × 109 /L Platelet count =75
× 109/L Serum bilirubin =1.5 x institutional upper limit of normal (ULN). This will
not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or
hepatic pathology), who will be allowed only in consultation with their physician.
AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver
metastases are present, in which case it must be =5x ULN
Measured creatinine clearance (CL) >60 mL/min or Calculated creatinine CL>60 mL/min by
the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection
for determination of creatinine clearance:
Males:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x serum creatinine (mg/dL)
Females:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x serum creatinine (mg/dL) x
0.85
9. Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.
10. Must have a life expectancy of at least 12 weeks
Exclusion Criteria:
1. Patients with EGFR mutations (identified with local testing).
2. Any prior treatment for NSCLC, including prior treatment with an anti-PD-1,
anti-PD-L1, anti-PD-L2, anti-CD137, anti-cytotoxic T-lymphocyte-associated antigen-4
(CTLA-4) antibody, chemo, RT, target therapy or investigational drug.
3. Concurrent enrolment in another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study
4. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria A. Patients with Grade =2 neuropathy will be evaluated on a case-by-case
basis after consultation with the Study Physician.
B. Patients with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab may be included only after consultation with the Study
Physician.
5. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone
replacement therapy) is acceptable.
6. Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of IP.
7. History of allogenic organ transplantation.
8. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., 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 are exceptions to this
criterion:
A. Patients with vitiligo or alopecia B. Patients with hypothyroidism (e.g., following
Hashimoto syndrome) stable on hormone replacement C. Any chronic skin condition that
does not require systemic therapy D. Patients without active disease in the last 5
years may be included but only after consultation with the study physician E. Patients
with celiac disease controlled by diet alone
9. 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, serious chronic
gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
situations that would limit compliance with study requirement, substantially increase
risk of incurring AEs or compromise the ability of the patient to give written
informed consent
10. History of another primary malignancy except for A. Malignancy treated with curative
intent and with no known active disease =5 years before the first dose of IP and of
low potential risk for recurrence B. Adequately treated non-melanoma skin cancer or
lentigo maligna without evidence of disease C. Adequately treated carcinoma in situ
without evidence of disease
11. History of leptomeningeal carcinomatosis
12. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) =470 ms
calculated from 3 ECGs (within 15 minutes at 5 minutes apart). Patient safety and the
cardiac SKG should be consulted as needed.
13. History of active primary immunodeficiency
14. Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and TB testing in line with
local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),
hepatitis CPatients with a past or resolved HBV infection (defined as the presence of
hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients
positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction
is negative for HCV RNA.
15. Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:
A. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection) B. Systemic corticosteroids at physiologic doses not to exceed 10
mg/day of prednisone or its equivalent C. Steroids as premedication for
hypersensitivity reactions (e.g., CT scan premedication)
16. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to
30 days after the last dose of IP.
17. Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy.
18. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
19. Prior randomisation or treatment in a previous durvalumab clinical study regardless of
treatment arm assignment.
20. Judgment by the investigator that the patient is unsuitable to participate in the
study and the patient is unlikely to comply with study procedures, restrictions and
requirements.
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