| Eligibility |
Inclusion Criteria:
Subject must meet all of the following applicable inclusion criteria to participate in this
study:
- Written informed consent and HIPAA authorization for release of personal health
information prior to registration. NOTE: HIPAA authorization may be included in the
informed consent or obtained separately.
- Age = 18 years at the time of consent.
- ECOG Performance Status 0 or 1 within 14 days prior to registration.
- Histologically and/or cytologically confirmed Stage III-IV recurrent or metastatic
NSCLC (American Joint Committee on Cancer (AJCC) Staging Manual 8th ed).
- Relapsed or refractory to immunotherapy. NOTE: anti-PD-1/PD-L1; prior anti-CTLA4
therapy is permitted; a minimum of 2 doses of prior immunotherapy is required. Prior
treatment with chemotherapy is permitted. Neoadjuvant or adjuvant therapy is
considered a line of treatment if given within 6 months of recurrent/metastatic
disease. No more than 2 prior lines of therapy is permitted (this does not include
oral targeted therapy).
- Patients with sensitizing EGFR, ALK, RET, ROS1, BRAF and MET exon 14 alterations must
have received at least one prior oral targeted therapy and prior chemotherapy (at
least one platinum doublet regimen, i.e., carboplatin/cisplatin plus pemetrexed/
paclitaxel/docetaxel/gemcitabine). NOTE: Oral targeted therapies do not count as lines
of treatment, with the exception of KRAS G12C agents (sotorasib, adagrasib, similar do
count toward lines of treatment). No more than 2 prior lines of therapy is permitted.
- Disease must be measurable by RECIST 1.1 criteria. Tumor lesions in a previously
irradiated area are considered measurable IF progression has been demonstrated in such
lesions after radiation.
- Demonstrate adequate organ function as defined in the table below. All screening labs
to be obtained within 14 days prior to C1D1.
- Hematological
- Absolute Neutrophil Count (ANC): =1500/µL
- Platelet Count: =100 000/µL
- Hemoglobin (Hgb): = 9 g/dL; Criteria must be met without erythropoietin
dependency and without packed red blood cell (pRBC) transfusion within last
2 weeks.
- Renal
---Serum creatinine OR Calculated creatinine clearance: = 1.5 × ULN OR = 30
mL/min for participant with creatinine levels >1.5 × institutional ULN
- Hepatic
- Total Serum Bilirubin: =1.5 ×ULN (Patients with known Gilbert Syndrome, a
total bilirubin = 3.0 x ULN, with direct bilirubin =1.5 × ULN)
- Aspartate aminotransferase (AST) AND Alanine aminotransferase (ALT): = 2.5 ×
ULN (=5 × ULN for participants with liver metastases)
- Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT)
Activated Partial Thromboplastin Time (aPTT): = 1.5 × ULN unless participant is
receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range
of intended use of anticoagulants
- Females of childbearing potential must have a negative urine or serum pregnancy test
at screening and within 72 hours of C1D1. See protocol for definition of childbearing
potential.
- Females of childbearing potential and males must be willing to abstain from
heterosexual intercourse or to use an effective method(s) of contraception as outlined
in protocol.
- As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures for the entire length of the study.
Exclusion Criteria:
Subjects meeting any of the criteria below may not participate in the study:
- Patients currently receiving anticancer therapies or who have received anticancer
therapies within 14 days prior to day 1 of study drug (including investigational
agents, chemotherapy, and antibody-based therapy).
- Radiation therapy within 14 days prior to day 1 of study drug. A 1-week washout is
permitted for palliative radiation (= 2 weeks of radiotherapy) to non-CNS disease.
- Intolerance to pembrolizumab or other PD-1/PD-L1 axis drug(s), or any other antibody
or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways,
including prior therapy with anti-tumor vaccines or other immune-stimulatory
anti-tumor agents.
- Known auto-immune conditions requiring systemic immune suppression therapy other than
prednisone =10 mg daily (or equivalent).
- History of (non-infectious) interstitial pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease.
- Receipt of allogeneic transplant (stem cell transplantation or solid organ).
- Current use of medications specified by the protocol as prohibited for administration
in combination with the study drugs. This includes patients with a condition requiring
systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents)
or other immunosuppressive medications within 14 days prior to day 1 of study drug.
Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone
equivalents are permitted in the absence of active autoimmune disease.
- Known history of HIV seropositivity or known acquired immunodeficiency syndrome
(AIDS), hepatitis C virus (allowed if received curative therapy), acute or chronic
active hepatitis B infection, or other serious chronic infection requiring ongoing
treatment. NOTE: no testing for Hepatitis B, Hepatitis C or HIV is required unless
mandated by local health authority.
- Current active infectious disease requiring systemic antibiotics, antifungal, or
antiviral treatment on Day 1 of study drug. Patients receiving prophylactic
antibiotics (e.g., for prevention of urinary tract infection or chronic obstructive
pulmonary disease) are eligible.
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study).
- Patients with a prior or concurrent malignancy whose natural history or treatment has
the potential to interfere with the safety or efficacy assessment of the
investigational regimen, per treating physician discretion, are not eligible for this
trial.
- Known active CNS metastases which are symptomatic. Eligible if metastases have been
locally treated 14 days prior to Cycle 1 Day 1, are clinically controlled, or
asymptomatic on Cycle 1 Day. Steroid dose must be equivalent of =10 mg prednisone
daily or equivalent dose steroid. Untreated, asymptomatic brain metastases allowed if
subject does not require corticosteroids or anticonvulsant therapy.
- History of myocardial infarction, NYHA class III or IV congestive heart failure, or
unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6
months prior to study enrollment.
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the
first dose of study drug. Administration of killed vaccines is allowed.
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