GT103 and Pembrolizumab for the Treatment of Patients with Recurrent or Refractory Stage III-IV Non-Small Cell Lung Cancer

Inclusion Criteria

• Written informed consent and Health Insurance Portability and Accountability Act (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
• Eastern Cooperative Oncology Group (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 edition [ed])
• Relapsed or refractory to immunotherapy. NOTE: anti-PD-1/PD-L1 is required; prior anti-CTLA4 therapy is permitted; a minimum of 2 doses of prior immunotherapy is required (patients must have received anti-PD-1/PD-L1 treatment; prior dual immune checkpoint therapy with anti-CTLA4 is allowed). 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 are permitted (this does not include oral targeted therapy)
• Patients with sensitizing EGFR, ALK, RET, ROS1 alterations must have received at least one prior tyrosine kinase inhibitor (TKI) and prior chemotherapy (at least one platinum doublet regimen; i.e. carboplatin/cisplatin plus pemetrexed/ paclitaxel/docetaxel/gemcitabine). No more than 2 prior lines of therapy is permitted (this does not include oral targeted therapy). BRAF and MET exon 14 alterations must have had prior oral targeted therapy
• Disease must be measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Tumor lesions in a previously irradiated area are considered measurable IF progression has been demonstrated in such lesions after radiation
• Absolute neutrophil count (ANC) >= 1500/uL (within 14 days prior to cycle 1 day 1 [C1D1])
• Platelet Count >= 100 000/uL (within 14 days prior to C1D1)
• Hemoglobin (Hgb) >= 9 g/dL (within 14 days prior to C1D1); Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
• Serum creatinine =< 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance >= 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN (within 14 days prior to C1D1)
• Bilirubin (total or direct): Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN (within 14 days prior to C1D1)
• Aspartate aminotransferase (AST) AND Alanine aminotransferase (ALT) =< 2.5 x ULN ( =<5 x ULN for participants with liver metastases) (within 14 days prior to C1D1)
• International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants (within 14 days prior to C1D1)
• Females of childbearing potential must have a negative urine or serum pregnancy test at screening and within 72 hours of C1D1
• Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use an effective method(s) of contraception
• 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

• 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- central nervous system (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 human immunodeficiency virus (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, New York Heart Association (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