Pembrolizumab + Imprime PGG for Metastatic Non-small Cell Lung Cancer After Progression on First-Line Therapy: Big Ten Cancer Research Consortium BTCRC-LUN15-017

Inclusion Criteria

• Male or female ≥ 18 years of age at time of consent.
• Subjects with histologically or cytologically confirmed non-small cell lung cancer (NCSLC).
• Subjects with stage IV non-small cell lung cancer as defined by American Joint Committee on Cancer (AJCC).
• Phase Ib: Subjects who progressed after first-line platinum-based chemotherapy and who are candidates for second-line therapy.
• Phase II: Subjects who have progressed on first-line systemic therapy (either platinum-based chemotherapy with or without immune checkpoint inhibitor or immune checkpoint inhibitor as first line therapy) who are candidates for second-line systemic therapy. Patients with early stage cancer will also be eligible if progression occurs:
• within 6 months of adjuvant chemotherapy after curative resection
• within 6 months of adjuvant chemotherapy after curative resection while on adjuvant immunotherapy, currently only available as part of a clinical trial
• within 6 months of curative surgery if chemotherapy is given in the neoadjuvant setting
• within 6 months of completion of chemoradiation (or 6 months from completion of consolidation chemotherapy if administered after concurrent chemoradiation)
• within 6 months of completion of chemoradiation or consolidation chemotherapy (if administered) while on consolidation immunotherapy, a setting for which durvalumab is FDA approved.
• Phase II: Subjects with an EGFR or ALK mutation who are no longer candidates for TKI therapy and have progressed on standard systemic therapy (either platinum-based chemotherapy with or without immune checkpoint inhibitor or immune checkpoint inhibitor as first line therapy).
• Phase II only: Measurable disease according to RECIST v1.1 (Section 8) obtained by imaging within 28 days prior to study registration. Phase Ib: subjects may enroll with or without measurable disease.
• Phase II only: Subjects must have presence of peripheral blood levels of IgG anti-β-glucan antibody (ABA) of ≥ 20 μg/mL as determined by an ELISA test within 90 days prior to study registration.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 within 28 days prior to study registration.
• Life expectancy of 6 months or greater as determined by the treating physician.
• Adequate hepatic function within 28 days prior to study registration defined as meeting all of the following criteria:
• total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN (except subject with Gilbert's Syndrome, who can have total bilirubin 3mg/dL, estimated glomerular filtration rate (GFR) ≥ 20 mL/min
• Adequate hematologic function within 28 days prior to study registration defined as meeting all of the following criteria:
• hemoglobin ≥ 9 g/dL; subjects requiring transfusion will be eligible to start study
• and absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• and platelet count ≥ 100 × 109/L
• Adequate coagulation functioning within 28 days prior to study registration defined by either of the following criteria:
• INR < 1.5 × ULN
• for subjects receiving anticoagulant, the subjects must, in the investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for subjects on warfarin should be in the therapeutic range. Low molecular weight heparin (LMWH) is allowed.
• Provided written informed consent and HIPAA authorization for release of personal health information, approved by an Institutional Review Board (IRB). NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Women of childbearing potential (WOCP) must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required within 72 hours of study registration. If the urine test cannot be confirmed as negative, a serum pregnancy test will be required.
• Women of childbearing potential (WOCP) must be willing to use two eff