| Eligibility |
Inclusion Criteria:
1. Patients with histologically confirmed NSCLC with the histology of sarcomatoid
carcinoma (WHO criteria for sarcomatoid carcinoma is used; carcinoma with spindle
and/or giant cells, pleomorphic carcinoma, spindle cell carcinoma, giant cell
carcinoma, carcinosarcoma, pulmonary blastoma). If the NSCLC patients showed
sarcomatoid carcinoma histology in re-biopsy sample (so called epithelial-mesenchymal
transition (EMT) phenomenon), such patients are eligible.
2. Age = 20 years at time of study entry.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Initial metastatic cases or recurrent cases after curative treatment (up to 2 previous
lines are allowed, and patients who experienced immune-checkpoint inhibitors are also
allowed).
5. A patient with at least one measurable lesion by RECIST1.1.
6. Asymptomatic brain metastasis. If patients have brain metastasis with neurological
symptom, they should be stabilized neurologically with prior radiotherapy or surgery
for the brain metastasis.
7. Body weight >40kg
8. Adequate normal organ and marrow function as defined below:
- Haemoglobin =9.0 g/dL
- Absolute neutrophil count (ANC) = 1,500 /mm3
- Platelet count =100,000 /mm3
- Serum bilirubin =1.5 x upper limit of normal (ULN).
- AST (SGOT)/ALT (SGPT) =2.5 x ULN unless liver metastases are present, in which
case it must be =5x ULN
- Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40
mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976)
9. Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients. Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:
Women <50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal treatments
and if they have luteinizing hormone and follicle-stimulating hormone levels in the
post-menopausal range for the institution or underwent surgical sterilization
(bilateral oophorectomy or hysterectomy). Women =50 years of age would be considered
post-menopausal if they have been amenorrheic for 12 months or more following
cessation of all exogenous hormonal treatments, had radiation-induced menopause with
last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year
ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral
salpingectomy or hysterectomy).
10. 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.
11. Must have a life expectancy of at least 12 weeks.
12. 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
Exclusion Criteria:
1. Participation in another clinical study with an investigational product during the
last 3weeks.
2. A patient with no measurable disease.
3. History of diverticulitis, intra-abdominal abscess, gastrointestinal obstruction,
abdominal carcinomatosis which are known risks factors for bowel perforation.
4. Active autoimmune disease within the past 2 years (NOTE: Subjects with vitiligo,
Grave's disease, or psoriasis not requiring systemic treatment -within the past 2
years- are not excluded) or a documented history of autoimmune disease or syndrome
that requires systemic steroids or immunosuppressive agents.
5. Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine
therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
antibodies) = 3 weeks prior to the first dose of study drug If sufficient wash-out
time has not occurred due to the schedule or PK properties of an agent, a longer
wash-out period will be required, as agreed by AstraZeneca/MedImmune and the
investigator.
6. 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.
1. Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after
consultation with the Study Physician.
2. Patients with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab may be included only after consultation with the Study
Physician.
7. Any concurrent chemotherapy, IP, or biologic therapy for cancer treatment. Concurrent
use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement
therapy) is acceptable.
8. Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of IP. Note: Local surgery of isolated lesions for palliative intent is
acceptable.
9. History of allogenic organ transplantation.
10. Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab, 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. 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:
1. Patients with vitiligo or alopecia
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
3. Any chronic skin condition that does not require systemic therapy
4. Patients without active disease in the last 5 years may be included but only
after consultation with the study physician
5. Patients with celiac disease controlled by diet alone
12. Uncontrolled current 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.
13. History of another primary malignancy except for
1. Malignancy treated with curative intent and with no known active disease =5 years
before the first dose of IP
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
3. Adequately treated carcinoma in situ without evidence of disease, NED =3 years
14. History of cytologically proven leptomeningeal carcinomatosis
15. QT interval corrected for heart rate using Fridericia's formula (QTcF) =470 ms
calculated from 3 ECG
16. A patient with clinically significant (i.e. active) heart disease (e.g.congestive
heart failure, symptomatic coronary artery diseases, cardiac arrhythmias, etc) or
myocardial infarction within past 12 months.
17. History of active primary immunodeficiency.
18. 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 C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients
with a past or resolved HBV infection (defined as the presence of hepatitis B core
antibody [anti-HBc] and absence of HBsAg) and with appropriate prophylactic antiviral
agents for positive HbsAg are eligible. Patients positive for hepatitis C (HCV)
antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
19. Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
20. 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.
21. 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 180 days after the last dose of durvalumab monotherapy.
22. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
23. 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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