PRIMARY OBJECTIVES:
I. To correlate circulating tumor DNA (ctDNA) levels measured using cancer personalized
profiling by deep sequencing (CAPP-Seq) with radiographic tumor assessments using Response
Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria in patients with
metastatic non-squamous non-small cell lung cancer (NSCLC) treated with pembrolizumab.
SECONDARY OBJECTIVES:
I. To correlate PD-L1 assessment on pre-treatment tumor samples with objective response
using RECIST v1.1 criteria in patients with metastatic non-squamous NSCLC treated with
pembrolizumab.
II. To determine the overall response rate (ORR) using RECIST v1.1 criteria in patients with
metastatic non-squamous NSCLC treated with pembrolizumab.
III. To determine the progression-free survival (PFS) using RECIST v1.1 in patients with
metastatic non-squamous NSCLC treated with pembrolizumab.
IV. To determine the overall survival (OS) in patients with metastatic non-squamous NSCLC
treated with pembrolizumab.
V. To determine the safety and tolerability of pembrolizumab in patients with metastatic
non-squamous NSCLC.
Inclusion Criteria:
- Has a pathologically proven recurrent or metastatic non-squamous non-small cell lung
cancer
- Previously received at least one line of prior systemic therapy for metastatic
disease; if the patient has a sensitizing EGFR mutation or ALK rearrangement, the
patient must have received at least one prior targeted therapy for metastatic disease
(ie, EGFR tyrosine kinase inhibitor [TKI] therapy or ALK TKI therapy, respectively);
there is no limit on prior therapies allowed; patients must have completed previous
treatment (including other investigational therapy) in greater than or equal to the
following times prior to initiation of trial treatment:
- Anti-cancer monoclonal antibody (mAb) therapy must be completed >= 3 weeks prior
to trial treatment
- Chemotherapy administered in a daily or weekly schedule must be completed >= 1
week prior to trial treatment
- Chemotherapy administered in an every 2-week schedule must be completed >= 2
weeks prior to trial treatment
- Chemotherapy administered in an every 3-week schedule must be completed >= 3
weeks prior to trial treatment
- Targeted small molecule therapy must be completed >= 1 week prior to trial
treatment
- Prior radiation therapy allowed as long as completed in the following times prior to
initiation of trial treatment:
- Definitive curative intent radiation >= 3 weeks prior to trial treatment
- Palliative body radiation >= 1 week prior to trial treatment
- Stereotactic brain radiation >= 1 week prior to trial treatment
- Whole brain radiation >= 2 weeks prior to trial treatment
- Patients with previously treated (with radiation or surgery) brain metastases that
are stable are allowed; patients with stable or progressing metastases must have
metastases =< 1.5 cm, be asymptomatic, and either not be on steroids or be on 10 mg
prednisone equivalent or less
- Has measurable disease based on RECIST v1.1 criteria
- Is medically able and willing to undergo needle biopsy of a tumor lesion; PD-L1
expression is not required to enroll in the trial
- Has life expectancy >= 3 months
- Ability to understand and the willingness to sign a written informed consent document
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Absolute neutrophil count (ANC) >= 1,000/mcL
- Platelets >= 75,000/mcL
- Hemoglobin >= 8 g/dL
- Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated
creatinine clearance >= 50 mL/min for patient with creatinine levels > 1.5 x
institutional ULN
- Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for patients with total
bilirubin levels > 1.5 ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x
ULN OR =< 5 x ULN for patients with liver metastases
- Female patients of childbearing potential must have a negative urine or serum
pregnancy test prior to the first dose of trial treatment; they must also agree to
two barrier methods or a barrier method plus a hormonal method, or agree to abstain
from heterosexual activity, for the course of the study through 120 days after the
last dose of trial treatment; females who have been surgically sterilized or are free
from menses for > 1 year (postmenopausal) may enroll
- Male patients with a female partner of childbearing potential should agree to use a
barrier method of contraception, or agree to abstain from heterosexual activity for
the course of the study through 120 days after the last dose of trial treatment
Exclusion Criteria:
- Is currently receiving another investigational therapy
- Has received prior anti-PD-1 or anti-PD-L1 therapy
- Has clinically significant toxicities from previous anti-cancer therapy that have not
resolved, or have not stabilized at a new baseline
- Has undergone a surgical procedure involving general anesthesia within 2 weeks of
starting trial treatment, or has inadequate healing or recovery from complications of
surgery prior to starting trial treatment; this does not apply to low-risk procedures
such as thoracentesis; paracentesis; chest tube/pleurX catheter placement; line
placement; needle biopsy of tumor; and bronchoscopy
- Is receiving high dose systemic steroid therapy within 3 days of trial treatment;
topical and intra-articular steroid injections are allowed, as are physiologic doses
of systemic steroids (=< 10 mg of prednisone equivalent daily)
- Has carcinomatous meningitis as determined by positive cerebrospinal fluid (CSF)
cytology
- Has known active additional malignancy that is undergoing active treatment
- Has active autoimmune disease that has required systemic treatment in the past 2
years (ie, with use of disease modifying agents, supra-physiologic doses of systemic
corticosteroids or immunosuppressive drugs); replacement therapy (eg, thyroxine,
insulin; or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment; asthma; type I
diabetes mellitus; hypothyroidism; and vitiligo are allowed
- Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
patient's participation for the full duration of the trial, or is not in the best
interest of the patient to participate, in the opinion of the treating investigator;
this includes known active tuberculosis; grade 3 active infection; history of
allogeneic bone marrow transplant or solid organ transplant; known history of human
immunodeficiency virus (HIV); known active hepatitis B (eg, hepatitis [Hep] B
deoxyribonucleic acid [DNA] positive in prior 3 months) or known active hepatitis C
(eg, hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected in
prior 3 months)
- Known active interstitial lung disease, or current (non-infectious) pneumonitis or
history of (non-infectious) pneumonitis that required oral steroids
- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of trial treatment