- Written informed consent and HIPAA authorization for release of personal health
information prior to registration. NOTE: HIPAA authorization may be included in the
informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- ECOG Performance Status of 0 or 1.
- Histological or cytological confirmation of stage III non-small cell lung cancer per
AJCC, 8th edition, eligible for curative-intent concurrent chemoradiation. NOTE:
subjects are not candidates for surgical resection either due to medical inoperability
or surgically unresectable disease.
- Measurable disease according to RECIST 1.1 criteria.
- Plan for treatment with concurrent chemoradiation with a dose of radiation ranging
from 54-66 Gy:
- Planned mean dose delivery to the lung <20 Gy
- V20 <35%
- No prior therapy for stage III NSCLC.
- Demonstrate adequate organ function as defined in the table below. All screening labs
to be obtained within 14 days prior to registration.
- Hemoglobin ≥ 9.0 g/dL
- White blood cell (WBC) ≥ 3,000/mm3
- Absolute neutrophil count (ANC) ≥ 1,500/mm3
- Platelet count ≥ 100,000/mm3
- Calculated creatinine clearance ≥ 40 mL/min
- Bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) ≤ 2.5 x institutional ULN
- Alanine aminotransferase (ALT) ≤ 2.5 x institutional ULN
- Females of childbearing potential must have a negative serum pregnancy test within 14
days prior to registration. NOTE: Females are considered of child bearing potential
unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal
ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least
12 consecutive months.
- Females of childbearing potential must be willing to abstain from heterosexual
activity or to use 2 forms of effective methods of contraception from the time of
informed consent until 180 days after treatment discontinuation. The two contraception
methods can be comprised of two barrier methods, or a barrier method plus a hormonal
- Men who are sexually active with WOCBP must use any contraceptive method with a
failure rate of less than 1% per year. Men receiving study drug and who are sexually
active with WOCBP will be instructed to adhere to contraception from the time of
informed consent and for a period of 180 days after treatment discontinuation.
- Life expectancy of at least 12 weeks per investigator discretion.
- As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures for the entire length of the study.
- Prior therapy for stage III NSCLC
- Mixed histology with small cell lung cancer will not be allowed.
- Sequential chemoradiation will not be permitted.
- Induction and consolidation chemotherapy (separate from concurrent chemoradiation)
will not be allowed.
- Prior exposure to anti-PD-1 or anti-PD-L1 antibodies including durvalumab.
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
- Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of
prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
- History of pulmonary fibrosis, interstitial lung disease, or pneumonitis requiring
- Active or prior documented autoimmune disease within the last 2 years. Patients with
vitiligo, stable hypothyroidism, Grave's disease, or psoriasis not requiring systemic
treatment are not excluded.
- Body weight < 30 kg
- Active and ongoing steroid use, except for non-systemically absorbed treatments (such
as inhaled or topical steroid therapy for asthma, COPD, allergic rhinitis).
- Active infection requiring systemic therapy.
- Uncontrolled current illness that in the opinion of the investigator renders the
investigational treatment plan unsafe.
- 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.
- 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.
- 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
- Active other malignancy; exceptions include basal cell or squamous cell skin cancer,
in situ cervical or bladder cancer.
- 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 Patients 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.
- Treatment with any investigational drug within 30 days prior to registration.
- History of organ transplantation (including allogeneic stem cell transplantation).
- Other medical or psychiatric conditions that in the opinion of the site investigator
would preclude safe participation in this protocol.
Eligibility Criteria for Consolidation Durvalumab
- Patients must have recovered from toxicities associated with prior chemoradiation to
CTCAE < Grade 2.
- Patients must not have progressed following chemoradiation therapy, as measured on
imaging per RECIST 1.1.
- Confirmation of ECOG Performance Status of 0 or 1.
- Any grade pneumonitis from prior chemoradiation will not be permitted.