SX-682 With Pembrolizumab for the Treatment of Metastatic or Recurrent Stage IIIC or IV Non-Small Cell Lung Cancer

Inclusion Criteria:

Subjects aged 18 years and older
Pathologically or cytologically confirmed non-small cell lung cancer with no known oncogenic EGFR mutation, ALK rearrangement, ROS1 rearrangement or RET fusions
Tumoral PD-L1 expression >=1% by any Clinical Laboratory Improvement Act (CLIA)-certified assay
Metastatic or recurrent non-small cell lung cancer (NSCLC). Stage IIIC per 8th edition TNM stage classification is allowed if not amenable to curative surgery or radiation per investigator judgment
At least one site of measurable disease as determined by the Investigator, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. Subjects must have ECOG PS 0 or 1 at the time of informed consent and at the time of treatment initiation
Must be willing to provide pre-treatment archived specimen or undergo a biopsy procedure if archived specimen is not available
Must be willing to provide an on-treatment biopsy, if deemed safe by the treating physician
Platelet count >= 100,000/uL
Absolute neutrophil count >= 1,500/uL
Hemoglobin >= 8g/dL
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times upper limit of normal
Creatinine =< 2.0 mg/dL
Women of child-bearing potential and sexually active men must agree to use adequate contraception (hormonal or barrier method) prior to treatment initiation, during treatment and for three months after completing treatment
Negative beta-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of childbearing potential. Pregnant or breast feeding women are not eligible
Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment

Exclusion Criteria:

Prior chemotherapy or immune checkpoint inhibitor or immune-modulatory therapy (e.g. anti-PD[L]1, anti-CTLA4, anti-TIM3, anti-GITR, anti-TIGIT, anti-LAG3), for metastatic or recurrent disease

Prior chemotherapy and immune checkpoint inhibitor and immune modulatory therapy in the curative setting is allowed as long as treatment was completed > 6 months prior to consenting
For patients with NSCLC harboring an oncogenic alteration other than listed may have received prior small molecule inhibitor therapy (e.g. MET inhibitor for MET exon 14 mutated NSCLC). A wash-out period of at least 5 half-lives is required prior to start of study treatment
Presence of other active cancers within the last 2 years. Patients with stage I cancer who have received definitive local treatment at least 2 years previously and no evidence of recurrence are eligible. All patients with previously treated in situ carcinoma are eligible, as patients with history of non-melanoma skin cancer

Symptomatic central nervous system (CNS) metastases; participants with known brain metastasis must be asymptomatic with no steroids or antiepileptics within 7 days prior to start of study treatment

Patients with untreated CNS metastases may be enrolled as long as they meet the above criteria. Patients with bulky CNS metastases should consider receiving radiation prior to study entry per investigator judgment
Participants with spinal cord compression must have received local treatment and must have been symptomatically stable with no use of steroids for at least 7 days prior to start of study treatment
Participants must not have an active autoimmune disease that has required immune modulating treatment within two years prior to consenting (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed
Known history of primary immunodeficiency
History of organ transplant that requires use of immunosuppressives
Current symptomatic pneumonitis and any past history of immune checkpoint inhibitor related pneumonitis regardless of steroid treatment history
History of non-infectious pneumonitis (e.g. radiation pneumonitis) that required steroids within 6 months of start of study treatment
Radiotherapy within 7 days of start of study treatment
Major surgery within 21 days of start of study treatment. Minor surgery within 2 weeks of start of study treatment. Placement of vascular access device and biopsies are not considered major or minor surgery and are allowed
Electrocardiogram (EKG) demonstrating a corrected QT (QTc) interval > 480 msec on three consecutive EKGs or patients with congenital long QT syndrome
Severe lung disease (e.g. chronic obstructive pulmonary disease [COPD]) who cannot stop steroids 7 days prior to start of study treatment

Serious cerebrovascular and cardiac disease defined as:

Active unstable angina pectoris
Congestive heart failure NYHA (New York Heart Association) > grade 3
Acute myocardial infarction within 3 months of consenting
Stroke or transient ischemic attack within 3 months of consenting

Known active chronic infections: Active hepatitis B, hepatitis C and tuberculosis. Testing is not required for assessment of eligibility. Active infection requiring IV antibiotics within 7 days of study treatment initiation

Hepatitis C virus (HCV) infection: Patients with known history of HCV infection are eligible if HCV viral load is below the limit of quantification per local assay
Hepatitis B virus (HBV) infection: Patients with known history of HBV infection are eligible if HBV viral load is below the limit of quantification and negative hepatitis B virus surface antigen (HBsAg) per local assay

Known uncontrolled HIV (human immunodeficiency virus) infection

Participants with known HIV infection are allowed if they are receiving anti-retroviral therapy, have CD4+ T-cell count >= 350 cells/uL within 6 months prior to study treatment initiation and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection
Any serious or uncontrolled concomitant disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study
Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent