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
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Phase
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male or female patients, ≥ 20 years of age
- Patients with NSCLC
- Patients whose disease has either responded or not progressed following 4-6 cycles of first-line induction chemotherapy.
- Patients with documented/confirmed intra-tumor positivity for HPV
- Patients with no major existing co-morbidities or medical conditions that will preclude administration of therapy, in the opinion of the Investigator
- Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
- Patients will use contraception during the study
- Patients with the ability to understand and give written informed consent for participation in this trial
Exclusion Criteria:
- Women who are pregnant or breast feeding
- Patients with histologically- or cytologically-confirmed squamous cell-classified NSCLC
- Patients with disease progression following first-line induction chemotherapy
- Patients with known active and uncontrolled central nervous system (CNS) or leptomeningeal metastases
- Patients with an active second primary malignancy or history of another malignancy
- Patients with inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy, including ≥ Grade 2 neuropathy
- 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
- Patients with evidence of inadequate organ function as defined in protocol
- Patients with a known allergy to both of the following antibiotics: ampicillin, trimethoprim-sulfamethoxazole
- Patients with a known allergy to anti-emetic medications and/or non-steroidal anti-inflammatory drugs (e.g., ibuprofen, naproxen, celecoxib)
- Patients with a history of severe hypersensitivity reaction to pemetrexed disodium (Alimta® or equivalent), or any of the excipients used in its formulation
- 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
- 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
- Patients with interstitial lung disease or active, non-infectious pneumonitis, active or prior documented inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis)
- Patients with an active infection requiring systemic therapy, prior to dosing with study drug
- 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
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: ADXS11-001 + Pemetrexed
|
Chemotherapy
ADXS11-001 is a live attenuated Listeria monocytogenes (Lm) bacteria bioengineered to secrete an antigen-adjuvant fusion protein (tLLO¬HPV-E7) consisting of a truncated fragment of the listeriolysin O (tLLO) fused to the full length E7 peptide of HPV-16.
|
|
Active Comparator: Pemetrexed Only
|
Chemotherapy
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Number of study participants with objective tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 and Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST)
Time Frame: 2 years
|
2 years
|
|
Number of study participants with progression free survival as assessed by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 and Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST)
Time Frame: 2 years
|
2 years
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Distribution of overall response rate (ORR) as assessed by RECIST v1.1 and irRECIST
Time Frame: 2 years
|
2 years
|
|
Distribution of duration of response (DR) as assessed by RECIST v1.1 and irRECIST
Time Frame: 2 years
|
2 years
|
|
Distribution of disease stabilization (SD) as assessed by RECIST v1.1 and irRECIST
Time Frame: 2 years
|
2 years
|
|
Distribution of overall survival (OS) as assessed by RECIST v1.1 and irRECIST
Time Frame: 2 years
|
2 years
|
|
Frequency and severity of treatment related adverse events (AEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03 for study participants on the combination arm
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
Sponsor
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Study Start
Primary Completion (Estimated)
Primary Completion
Study Completion (Estimated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Estimated)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antineoplastic Agents
- Folic Acid Antagonists
- Pemetrexed
Other Study ID Numbers
Other Study ID Numbers
- GBP-11-201
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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