- 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 obtained
from the patient/legal representative prior to performing any protocol- related
- Patient age ≥ 18 at time of consent
- Early stage NSCLC (Stage I to IIIA; T1-4 excluding patients with satellite nodules in
the same or ipsilateral lobes, N0; AJCC 8th edition)
- Ineligible for or unwilling to undergo surgical resection. Reasons for surgical
ineligibility include: medically inoperable or surgically unresectable (due to tumor
size, location etc.), as assessed by MSKCC thoracic surgeon or multi-disciplinary
tumor board consensus. Reasons for ineligibility or patient's unwillingness to undergo
surgical resection must be clearly documented.
- Histological and/or cytological confirmation of NSCLC as per standard of care biopsy;
no additional research protocol-specific biopsy is needed.
- ECOG/WHO PS 0-1 (KPS 70-100)
- Candidates for definitive SBRT
° If, after candidates have been planned for RT, they are unable to be treated with
the institutional dose constraints as listed in the appendix, they will be labeled
ineligible and removed from the study. Ineligible patients will be replaced.
- A PFS of <60% (at least 40% risk for disease progression) at 2 years based on an
MSKCC-developed risk prediction model (see section 9.0).
- Body weight > 30kg
- Adequate normal organ and marrow function as defined below:
- Hemoglobin ≥9.0 g/dL
- Absolute neutrophil count (ANC) 1.5 x (> 1500 per mm^3)
- Platelet count ≥75 x 10^9/L (>75,000 per mm^3)
- 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
- AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients. Women will be considered postmenopausal 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 postmenopausal 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
- Must have a life expectancy of at least 12 weeks
- Participation in another clinical study with an investigational product during the
last 4 weeks.
- Previous thoracic radiation precluding definitive SBRT to the current tumor.
- 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
1. Patients with vitiligo or alopecia
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
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 PI
5. Patients with celiac disease controlled by diet alone
- 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
1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after
consultation with the PI.
2. Patients with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab may be included only after consultation with the PI.
- Prior/Current Therapies:
1. Treatment with a monoclonal antibody within 4 weeks prior to study Day 1 or has
not recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to agents
administered > 4 weeks earlier (intraocular bevacizumab is acceptable).
2. Prior chemotherapy or targeted small molecule therapy, within 3 weeks prior to
study Day 1 or has not recovered (i.e., ≥ Grade 1 at baseline) from adverse
events due to a previously administered agent).
3. Prior therapy with an anti-PD-1, anti-PD-L1, including durvalumab, anti-PDL2,
anti-CD137, anti-Cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4) antibody,
or any other antibody or drug specifically targeting T-cell co-stimulation or
4. Current or prior use of immunosuppressive medication within 14 days before the
first dose of durvalumab. The following are exceptions to this criterion:
i. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection) ii. Systemic corticosteroids at physiologic doses not to exceed
<<10 mg/day>> of prednisone or its equivalent iii. Steroids as premedication for
hypersensitivity reactions (e.g., CT scan premedication) e. 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. f. Prior chemotherapy for this diagnosis of lung cancer
- 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
- History of allogenic organ transplantation.
- Severe concurrent illness:
1. Known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
2. Known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of
the skin, or in situ cervical cancer that has undergone potentially curative
3. 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) are
eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV RNA.
4. Active infection requiring systemic therapy.
5. Evidence of interstitial lung disease or active, non-infectious pneumonitis.
6. Clinically significant (i.e., active) cardiovascular disease: symptomatic
cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial
infarction (< 6 months prior to enrollment), unstable angina, congestive heart
failure (≥ New York Heart Association Classification Class II), or serious
cardiac arrhythmia requiring medication.
- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ a highly effective birth control
from screening to 90 days after the last dose of durvalumab monotherapy.
a. Highly effective methods of contraception, defined as one that results in a low
failure rate (ie, less than 1% per year) when used consistently and correctly are
described in Appendix B. Note that some contraception methods are not considered
highly effective (e.g. male or female condom with or without spermicide; female cap,
diaphragm, or sponge with or without spermicide; non-copper containing intrauterine
device; progestogen-only oral hormonal contraceptive pills where inhibition of
ovulation is not the primary mode of action [excluding Cerazette/desogestrel which is
considered highly effective]; and triphasic combined oral contraceptive pills).
- Live vaccination within 4 weeks prior to the first dose of durvalumab and while on
trial is prohibited except for administration of inactivated vaccines.
- Connective tissue disorders or idiopathic pulmonary fibrosis involving the lungs
- Known actionable EGFR or ALK mutation
- Known contraindications to radiotherapy
- History of leptomeningeal carcinomatosis
- History of active primary immunodeficiency
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug
- Prior randomization or treatment in a previous durvalumab clinical study regardless of
treatment arm assignment.
- Participants must not donate blood while on durvalumab therapy.