The purpose of stage 1 of the study is to find out if blood tests can be used to see how the
cancer is responding to treatment with pembrolizumab.
The standard or usual treatment for this disease is pembrolizumab given by needle every three
weeks. This study will be done in two stages.
The purpose of stage 1 of the study is to find out if we can use blood tests to see how the
cancer is responding to treatment with pembrolizumab. A second stage of the study will take
place once stage 1 is completed. In stage 2 blood tests will be used to help determine if
patients whose cancer does not seem to be getting better on treatment with pembrolizumab,
would do better on a different treatment.
- Histologically or cytologically confirmed stage IV non-squamous NSCLC (includes M1a,
M1b, and M1c stage disease, AJCC 8th edition). Patients with T4NX disease (Stage IIIB)
with nodule in ipsilateral lung lobe are eligible if they are not candidates for
combined chemotherapy and radiation. Patients with Large Cell Neuroendocrine Carcinoma
(LCNEC) are not eligible.
- Confirmed EGFR and ALK mutation negative disease
- Patients must have a PD-L1 test result from a certified laboratory indicating PD-L1
expression Tumour Proportion Score (TPS) ≥ 50%.
- No prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC.
Chemotherapy for non-metastatic disease (e.g. adjuvant therapy) or immunotherapy for
locally advanced Stage III disease is allowed if at least 6 months have elapsed since
the prior therapy and enrollment. Local therapy, e.g. palliative radiation, is allowed
as long as a period of 2 weeks has passed since completion.
- Patients must have recovered to ≤ grade 1 from all reversible toxicity related to
prior systemic or radiation therapy.
- Previous major surgery is permitted provided that surgery occurred at least 28 days
prior to patient enrollment and that wound healing has occurred.
- Eligible to receive treatment with pembrolizumab according to the guidance/indications
described in the Product Monograph (Canada) or Drug Label (U.S.). Reimbursement of
pembrolizumab may not be uniform across all sites. In the event that the
site/investigator is unable to provide access to the drug, the patient will not be
eligible for this trial.
- Must be ≥ 18 years of age.
- ECOG performance status 0 or 1.
- Clinically and/or radiologically documented disease with at least one lesion
measurable as defined by RECIST 1.1.
- Imaging investigations including CT of the chest, abdomen and pelvis and MRI of the
brain (if known brain metastases) or other scans as necessary to document all sites of
disease must be done within 28 days prior to enrollment.
- Adequate hematology and organ function as defined below (must be done within 14 days
prior to enrollment).
- White Blood Cells ≥ 2.0 x 10^9/L (2000/μL)
- Absolute neutrophils ≥ 1.5 x 10^9/L (1500/μL)
- Platelets ≥ 100 x 10^9/L (100 x 10^3/μL)
- Bilirubin ≤ 1.5 x ULN (upper limit of normal)*
- AST and/or ALT ≤ 3 x ULN, < 5 x ULN for patients with liver metastases
- Serum creatinine or Creatinine clearance ≤ 1.5 x ULN OR ≥ 40 mL/min
- Patients must consent to provision of, and investigator must confirm access to and
agree to submit, a representative archival formalin-fixed paraffin block of tumour
tissue for correlative analyses when tumour tissue is available.
Patients must consent to collection of liquid biopsy (blood) samples for ctDNA analysis by
CLIA central laboratory and for correlative analysis by a research central laboratory.
- Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements. Each patient must sign a consent form prior to enrollment to
the trial to document their willingness to participate.
- Patients must be accessible for treatment and follow-up. Investigators must assure
themselves the patients enrolled on this trial will be available for complete
documentation of the treatment, adverse events, collection of blood samples, response
assessments and follow-up. Patients must agree to return to their primary care
facility for response assessments as well as any adverse events which may occur
through the course of the trial.
- In accordance with CCTG policy, protocol treatment with pembrolizumab is to begin
within 2 working days of patient enrollment.
- Women/men of childbearing potential must have agreed to use a highly effective
contraceptive method. Women of childbearing potential will have a pregnancy test to
determine eligibility as part of the Pre-Study Evaluation.
- Patients with a prior malignancy whose natural history or treatment does not have the
potential to interfere with the safety or efficacy assessment of the investigational
regimen are eligible for this trial.
- Patients with brain metastases or leptomeningeal metastases are eligible if these have
been treated and follow up brain imaging shows no evidence of progression or if the
treating physician determines that immediate CNS specific treatment is not required
and is unlikely to be required during the first cycle of therapy. There must also be
no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day
- History of primary immunodeficiency or history of allogeneic organ transplant that
requires therapeutic immunosuppression and the use of immunosuppressive agents within
14 days of study drug administration.
- Active or prior documented autoimmune or inflammatory disorders. Included are
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.
Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to
autoimmune condition only requiring hormone replacement, psoriasis not requiring
systemic treatment, or conditions considered to be of low risk for recurrence are
permitted to enroll.
- 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 to:
- 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
tuberculosis or any infection requiring systemic therapy).
- Active peptic ulcer disease or gastritis.
- Active pneumonitis.
- Concurrent treatment with other anti-cancer therapy or other investigational
- Patients who have experienced untreated and/or uncontrolled cardiovascular conditions
and/or have symptomatic cardiac dysfunction (including 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 known history or current symptoms of cardiac
disease, or history of treatment with cardiotoxic agents, should have a clinical risk
assessment of cardiac function using the New York Heart Association Functional
Classification. To be eligible for this trial, patients should be class 2B or better.
- Pregnant or lactating women.
- Men who are sexually active with women of childbearing potential and women of
childbearing potential must agree to use adequate contraception.