Combinations of durvalumab and tremelimumab have also been studied. While the combination has
been studied in over 200 people, it is not clear if it can offer better results when it is
combined with chemotherapy.
Recently, immunotherapies that target the PD-1/PD-L1 axis have shown promise in treating
patients with non-small cell lung cancer.
- Patients must have histologically and/or cytologically confirmed diagnosis of squamous
or non-squamous, non-small cell carcinoma of the lung. Patients with poorly
differentiated tumours will only be eligible if NSCLC is confirmed by
immunohistochemistry markers (TTF1/P63 or P40/CK5). Patients with known sensitizing
EGFR mutations or known ALK-fusion are not eligible.
- Patients must have stage IV disease according to the 8th TNM version staging.
- Patients must have an adequate histopathology specimen and must consent to release
this specimen for protocol required testing. This is a mandatory component of the
- Patient must consent to provision of samples of blood in order that the specific
correlative marker assays proscribed may be conducted.
- All patients must have measurable disease as defined by RECIST 1.1 All radiology
studies must be performed within 28 days prior to randomization (within 35 days if
The criteria for defining measurable disease are as follows:
- CT scan (with slice thickness of 5 mm) ≥ 10 mm --> longest diameter
- Physical exam (using calipers) ≥ 10 mm
- Lymph nodes by CT scan ≥ 15 mm --> measured in short axis
Measurable lesions must be outside a previous radiotherapy field if they are the sole site
of disease, unless disease progression has been documented.
- Patients must be 18 years of age or older.
- ECOG performance status of 0 or 1.
- Absolute neutrophils ≥ 1.5 x 10^9/L
- Platelets ≥ 100 x 10^9/L
- Hemoglobin ≥ 90 g/L
- Bilirubin ≤ 1.5 x UNL (upper limit of normal)
- AST and ALT ≤ 2.5 x UNL (if liver metastases are present, ≤5 x UNL) Creatinine < 1.25
UNL or Creatinine clearance ≥ 45 mL/min
- Cytotoxic Chemotherapy: Patients may not have received prior cytotoxic chemotherapy
for advanced/metastatic disease.
- Adjuvant Chemotherapy: Patients may have had prior adjuvant therapy for completely
resected disease, providing it has been completed at least 12 months prior to
- Patients treated with concurrent chemotherapy/radiation regimens for unresectable
locally advanced Stage III disease will be eligible providing it has been completed at
least 12 months prior to randomization.
- Other Systemic Therapy: Patients may not have received prior EGFR or alk inhibitors.
Patients may not have received prior treatment with immune-based therapy, including
durvalumab and tremelimumab vaccines or oncolytic viral therapy. Patients must have
recovered from any reversible treatment related toxicities prior to randomization.
- Prior external beam radiation is permitted provided a minimum of 14 days (2 weeks)
have elapsed between the last dose of radiation and date of randomization. Concurrent
radiotherapy is not permitted.
Patients must have recovered from any acute toxic effects from radiation prior to
- Patients must have recovered from any acute toxic effects from radiation prior to
- Surgery: Previous surgery is permitted provided that wound healing has occurred and at
least 14 days have elapsed (major surgery) prior to randomization.
- Patient must be able (i.e. sufficiently fluent) and willing to complete the quality of
life and health economics questionnaires.
- Patient consent must be appropriately obtained in accordance with applicable local and
- Patients must be accessible for treatment and follow-up. All randomized patients must
be followed and treated at participating centres.
- In accordance with CCTG policy, protocol treatment is to begin within 2 working days
of patient randomization.
- Female patients of childbearing potential who are sexually active with a
non-sterilized male partner must use at least one highly effective method of
contraception while on study and for 6 months after the last dose of durvalumab and
tremelimumab or for 3 months after the last dose of durvalumab alone
- Patients with a history of other malignancies, except: adequately treated non-melanoma
skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
curatively treated with no evidence of disease for ≥ 3 years. Patients with a history
of other malignancies detected at an early stage and whom the investigator believes
have been curatively treated and are at low risk of recurrence MAY be eligible.
Contact CCTG to discuss eligibility prior to enrolling.
- 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, celiac disease or other serious gastrointestinal chronic
conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid
arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of
treatment. The following are exceptions to this criterion:
- Patients with alopecia.
- Patients with Grave's disease, vitiligo or psoriasis not requiring systemic
treatment (within the last 2 years).
- Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on
- History of primary immunodeficiency, history of allogenic organ transplant that
requires therapeutic immunosuppression and the use of immunosuppressive agents within
28 days of randomization* or a prior history of severe (grade 3 or 4) immune mediated
toxicity from other immune therapy or grade ≥ 3 infusion reaction.
- Live attenuated vaccination administered within 30 days prior to randomization
- History of hypersensitivity to durvalumab or tremelimumab or any excipient. Patients
who have received other treatment or other antibodies must not have had intolerable
toxicity or required steroids to manage toxicity.
- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec
in screening ECG measured using standard institutional method or history of familial
long QT syndrome.
- Patients who have untreated and/or uncontrolled cardiovascular conditions and/or have
symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial
infarction within the previous year or cardiac ventricular arrhythmias requiring
medication, history of 2nd or 3rd degree atrioventricular conduction defects).
Patients with a significant cardiac history, even if now controlled, should have a
LVEF ≥ 45%. (Note: patients with uncomplicated controlled hypertension do not require
LVEF measurement in the absence of other significant cardiac history)
- Concurrent treatment with other investigational drugs or anti-cancer therapy
- Patients with untreated brain or meningeal metastases are not eligible. Patients with
treated CNS disease who have radiologic AND clinical evidence of stable brain
metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are
eligible providing that they are asymptomatic and do not require corticosteroids (must
have discontinued steroids at least 1 week prior to randomization).
- Pregnant or Lactating Women: Women of childbearing potential must have a pregnancy
test (urine or serum) proven negative within 14 days prior to randomization. If urine
test is positive, pregnancy testing may then include an ultrasound to rule-out
pregnancy if a false-positive is suspected. For example, when beta-human chorionic
gonadotropin is high and partner is vasectomized, it may be associated with tumour
production of hCG, as seen with some cancers. Patient will be considered eligible if
an ultrasound is negative for pregnancy. Men and women of child-bearing potential must
agree to use adequate contraception.
- Patients with serious illnesses or medical conditions which would not permit the
patient to be managed according to the protocol (including corticosteroid
administration), or would put the patient at risk. This includes but is not limited
- Contraindications to the use of pemetrexed, gemcitabine, cisplatin and/or
carboplatin (consult product monograph);
- History of significant neurologic or psychiatric disorder which would impair the
ability to obtain consent or limit compliance with study requirements;
- Active infection requiring systemic therapy; (including any patient known to have
active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or
- Active peptic ulcer disease or gastritis;
- Known pneumonitis or pulmonary fibrosis with clinically significant impairment of