| Eligibility |
Inclusion Criteria:
- 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
procedures, including screening evaluations.
- Patient age = 18 at time of consent
- Stage IIIA-C NSCLC (as per the American Joint Commission on Cancer (AJCC) 8th edition)
- Not a candidate for surgical resection as determined by one or more of the following
criteria in multidisciplinary evaluations: technically unresectable, medically
inoperable, patient declines operative approach
- Candidate for concurrent chemoradiation therapy as determined by the treating
radiation and thoracic oncologist
- Histologic confirmation of NSCLC with pathological review done at MSK
- ECOG Performance Status 0-1
- Candidate for definitive thoracic radiation (defined 60Gy ± 10% in 2 Gy fractions)
- Body weight > 30 kg
- Adequate normal organ and marrow function as defined below:
- Hemoglobin =9.0 g/dL
- Absolute neutrophil count (ANC) 1.5 x (> 1500 per mm3)
- Platelet count =100 x 10^9/L (>100,000 per mm3)
- 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
- Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40
mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour
urine collection for determination of creatinine clearance
- 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 amenorrhoeic 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
amenorrhoeic 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
amenorrhoeic 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).
- 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.
- Must have a life expectancy of at least 6 months
Exclusion Criteria:
- Participation in another clinical study with an investigational (non-FDA approved)
product during the last 4 weeks
- Concurrent enrollment in another clinical study for lung cancer, unless it is an
observational (non-interventional) clinical study or during the follow-up period of an
interventional study
- Previous thoracic radiation precluding definitive RT
- Contraindication to Durvalumab
- 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:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients not on biologic therapy without active disease in the last 3 years may
be included but only after consultation with the study physician
- Patients with celiac disease controlled by diet alone
- Prior/Current Therapies:
- Treatment with a administered > 4 weeks earlier (intraocular bevacizumab is
acceptable).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
- Patients receiving biologic drugs targeting the immune system (e.g. TNF blockers,
anakinra, abatacept, tocilizumab) within 4 weeks prior to study Day 1
- Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137,
anti-Cytotoxic Tlymphocyte-associated antigen-4 (CTLA-4) antibody, or any other
antibody or drug specifically targeting T-cell co-stimulation or checkpoint
pathways.
- Prior treatment with canakinumab
- Current or prior use of a systemic immunosuppressive medication within 14 days
before the first dose of canakinumab. 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 for less than 30 days. iii.
Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication) iv. Systemic glucocorticoid replacement for conditions such as
adrenal or pituitary insufficiency.
- Major surgical procedure (e.g. intra-cranial, intra-thoracic, intra-abdominal, or
intra-pelvic) within 28 days prior to the first dose of canakinumab
- Prior history of malignant disease, other than this NSCLC, that has been diagnosed
and/or required therapy within the past 3 years. Exceptions to this exclusion include:
completely resected basal cell and squamous cell skin cancers, completely resected
carcinoma in situ of any type, and definitely treated Stage 0-I breast cancers on
hormonal maintenance therapy or definitely treated Stage I-IIA prostate cancer.
- History of allogenic organ transplantation.
- Known severe concurrent illness:
- Known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- Active or recurrent hepatic disorders including cirrhosis, hepatitis B and 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.
- Active tuberculosis infection (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and TB testing in line
with local practice)
- Human Immunodeficiency Virus (positive HIV 1/2 antibodies).
- Active infection requiring systemic therapy.
- Evidence of interstitial lung disease or active, non-infectious pneumonitis.
- 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 unless they are willing to employ a highly effective birth
control from screening to 130 days after the last dose of canakinumab.
°Highly effective methods of contraception, defined as one that results in a low
failure rate (i.e., less than 1% per year) when used consistently and correctly Note
that condom use during intercourse among sexually actives males will be required. Note
that some contraception methods are not considered highly effective (e.g. 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).
- Connective tissue disorders involving the lung(s) and/or esophagus requiring active
treatment or idiopathic pulmonary fibrosis
- Known history of active primary immunodeficiency
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
- Receipt of live vaccination within 3 months prior to the first dose of study durg.
Note that this only applies to live vaccines.
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