A Study of Pemetrexed Maintenance With or Without ADXS11-001 Immunotherapy in Patients With Human Papillomavirus Positive (HPV+), NSCLC Following First-Line Induction Chemotherapy

A Phase 2, Open-label, Randomized, Parallel Group, Controlled Study of Pemetrexed Maintenance With or Without ADXS11-001 Immunotherapy in Patients With Human Papillomavirus-Positive, Non-Squamous, Non-Small Cell Lung Carcinoma Following First-Line Induction Chemotherapy

• Open label
• Enrollment in the order of confirmation of eligibility and HPV+ tumor status
• Prospective stratification based on 3 factors, epidermal growth factor receptor (EGFR) mutation status, performance status and first-line induction chemotherapy outcome;
• Randomization (2:1 ratio): (82 patients receiving the combination of pemetrexed plus ADXS11-001 vs. 42 patients receiving pemetrexed alone)
• Treatment Arm: Pemetrexed plus ADXS11-001 immunotherapy
• Control Arm: Pemetrexed only
• Positive control: pemetrexed chemotherapy

Inclusion Criteria:

1. Male or female patients, ≥ 20 years of age
2. Patients with NSCLC
3. Patients whose disease has either responded or not progressed following 4-6 cycles of first-line induction chemotherapy.
4. Patients with documented/confirmed intra-tumor positivity for HPV
5. Patients with no major existing co-morbidities or medical conditions that will preclude administration of therapy, in the opinion of the Investigator
6. Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
7. Patients will use contraception during the study
8. Patients with the ability to understand and give written informed consent for participation in this trial

Exclusion Criteria:

1. Women who are pregnant or breast feeding
2. Patients with histologically- or cytologically-confirmed squamous cell-classified NSCLC
3. Patients with disease progression following first-line induction chemotherapy
4. Patients with known active and uncontrolled central nervous system (CNS) or leptomeningeal metastases
5. Patients with an active second primary malignancy or history of another malignancy
6. Patients with inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy, including ≥ Grade 2 neuropathy
7. Patients with inadequate recovery from any previous surgical procedure, or patients having undergone any major surgical procedure within 4 weeks prior to the start of study treatment
8. Patients with evidence of inadequate organ function as defined in protocol
9. Patients with a known allergy to both of the following antibiotics: ampicillin, trimethoprim-sulfamethoxazole
10. Patients with a known allergy to anti-emetic medications and/or non-steroidal anti-inflammatory drugs (e.g., ibuprofen, naproxen, celecoxib)
11. Patients with a history of severe hypersensitivity reaction to pemetrexed disodium (Alimta® or equivalent), or any of the excipients used in its formulation
12. Patients with a history of an autoimmune disorder requiring systemic treatment within the past 3 months, or a documented history of a clinically severe autoimmune disease or a syndrome that requires systemic steroid or immunosuppressive agents
13. Patients with a known immunodeficiency including patients: with HIV infection, who have undergone previous organ transplantation and require immunosuppressive therapy or long-term immunosuppressive therapy for any other reason
14. Patients with interstitial lung disease or active, non-infectious pneumonitis, active or prior documented inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis)
15. Patients with an active infection requiring systemic therapy, prior to dosing with study drug
16. Patients with any other life-threatening illness, uncontrolled medical condition (e.g., elevated troponin or creatinine; uncontrolled diabetes), significant organ system dysfunction, or clinically significant laboratory abnormality, which in the opinion of the Investigator would either compromise the patient's safety or interfere with evaluation of the study treatment
17. Patients with a psychiatric disorder, substance abuse disorder, or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary study-related evaluations
18. Patients with a history of or current evidence of any condition, therapy, or laboratory abnormality that might: confound the results of the trial, interfere with the patient's participation in the trial, or suggest that participation in the trial is not in the best interest of the patient, in the opinion of the treating investigator