Study of ADXS-503 With or Without Pembro in Subjects With Metastatic Non-Small Cell Lung Cancer

Exclusion Criteria

• •1. Subject has an ongoing different primary malignancy. Exceptions include treated basal cell carcinoma of the skin or squamous cell carcinoma of the skin;
• •2. Subject has an active autoimmune disease requiring systemic treatment within the past 3 months, a documented history of clinically severe autoimmune disease, or a disorder that requires systemic corticosteroids or immunosuppressive agents. Subjects with vitiligo, psoriasis, alopecia or resolved childhood asthma/atopy not requiring systemic treatment would be an exception to this rule. Subjects with hypothyroidism who are stable on hormone replacement (\>10 mg daily prednisone equivalent) or Sjögren's syndrome will not be excluded from the study;
• •3. Subject has a diagnosis of primary immunodeficiency, is dependent on or has received systemic corticosteroid therapy (\>10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study treatment. Inhaled or topical corticosteroids, and adrenal replacement corticosteroid doses \>10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease;
• •4. Subject has neuropathy (sensory or motor) ≥Grade 3 per CTCAE v4.03;
• •5. Subject has had an allogeneic tissue/solid organ transplant;
• •6. Subject has interstitial lung disease (ILD) OR has had a history of pneumonitis that has required oral or IV steroids;
• •7. Subject has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (no new or enlarging brain metastases) by imaging for at least 2 weeks following treatment, and clinically stable with no symptoms due to CNS metastasis, and are not using corticosteroids for at least 14 days prior to the start of study treatment;
• •8. Subject has a concurrent unstable or uncontrolled medical condition (e.g., active uncontrolled systemic infection, unstable angina, congestive heart failure, uncontrolled diabetes) or other chronic disease, which in the opinion of the Investigator could compromise the subject or the study;
• •9. Subject has a known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies);
• •10. Subject has a known active hepatitis B (e.g., HBsAg reactive) or hepatitis C infection (e.g., HCV RNA \[qualitative\] is detected) or tuberculosis;
• •11. Subject has an active infection requiring systemic therapy or is dependent on or currently receiving antibiotics that cannot be discontinued before dosing. (Note: Subjects who discontinue an antibiotic prior to dosing must wait at least 5 half-lives after the last dose of antibiotic before receiving any study treatment);
• •12. Subject has known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the study;
• •13. Subject has an implanted medical device that poses a high risk for bacterial colonization and/or that cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screws, metal plates, bone grafts, or other exogenous implants). NOTE: More common devices and prosthetics that include arterial and venous stents, dental and breast implants and venous access devices (e.g., Port-a-Cath or Mediport) are permitted. Sponsor must be contacted prior to consenting any subject who has any other device or implant;
• •14. Subject is pregnant or breastfeeding, or plans to become pregnant or to father children, from the Screening visit through at least 120 days after the final dose of study treatment;
• •15. Subject has a contraindication (e.g., sensitivity/allergy) to trimethoprim/ sulfamethoxazole and ampicillin;
• •16. Subject has a contraindication to non-steroidal anti-inflammatory drugs (NSAIDs);
• •17. Subject has a known allergy to any component of the study formulation(s);
• •18. Subject has a history of listeriosis;
• •19. Subject has any other serious or uncontrolled physical or mental condition/disease that, as judged by the Investigator, could place the subject at higher risk derived from their participation in the study, could confound results of the study, or would be likely to prevent compliance with the requirements of the study;
• •20. Subject has received chemotherapy and/or radiation therapy (except palliative radiation therapy for disease-related pain) within 2 weeks of the first dose of study treatment;
• •21. Subject has received monoclonal antibody or other biologic therapy within 5 half-lives or 28 days prior to the first dose of study treatment, whichever is shorter. An exception to this exclusion criterion will be pembrolizumab monotherapy for subjects enrolled in Part B;
• •22. Subject has received prior treatment with an Lm-based immunotherapy;
• •23. Subject is receiving or plans to receive future treatment with PI3K or TNFα inhibitors;
• •24. Subject has received a live vaccine within 30 days prior to the first dose of study treatment;
• •25. Subject has not recovered to baseline from AEs, with the exception of alopecia, due to previously administered agent(s);
• •26. Subject has had major surgery within 6 weeks prior to the initiation of study treatment. NOTE:
• •All surgical complications must have recovered to baseline or Grade ≤1 prior to the initiation of study therapy. Sponsor must be consulted prior to enrolling subjects on the study who recently had a major surgery or have a new artificial implant, and/or devices;
• •27. Subject is currently participating in or has participated in a study of an investigational agent(s) within 4 weeks of the first dose of study treatment;
• •28. Subject is or has an immediate family member (spouse or children) who, as investigational site or sponsor staff, is directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject;
• •29. In Part C, subject has received systemic therapy for the treatment of their metastatic NSCLC.
• •Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease;
• •30. In Part C, subject has an EGFR sensitizing mutation and/or an ALK translocation;
• •31. In Part C, baseline tumor specimen is not evaluable for PD-L1 expression by the central laboratory. If an additional tumor specimen is submitted AND evaluable for PD-L1 expression, the subject will be eligible to participate if PD-L1 expression is assessed as ≥50% by the central laboratory;
• •32. In Part C, subject has received prior systemic chemotherapy, biological therapy, OR major surgery within 6 weeks of the first dose of study treatment; received thoracic radiation therapy of \>30 Gy within 6 months of first dose of study treatment;
• •33. In Part C, subject has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti- CD137, or anti-CTLA-4 antibody, or any other antibody or drug that specifically targets T cell co-stimulation or immune checkpoint pathways.