A Phase 2 Study of Viagenpumatucel-L (HS-110) in Patients With Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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Determine whether viagenpumatucel-L combined with low-dose cyclophosphamide prolongs survival in patients with NSCLC who failed 2 or 3 prior lines of therapy for incurable or metastatic disease compared with chemotherapy alone.

Detailed Description
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This study will test whether vaccination with viagenpumatucel-L combined with low-dose cyclophosphamide will prolong the survival of patients with non-small cell lung cancer (NSCLC) who have failed 2 or 3 prior lines of therapy for incurable or metastatic disease compared with chemotherapy alone. Patients will be randomized 2 to 1 into the viagenpumatucel-L arm and the chemotherapy alone arm, respectively.

Official Title
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A Phase 2, Multicenter, Randomized Study to Evaluate the Safety and Efficacy of Viagenpumatucel-L (HS-110) in Combination With Low Dose (Metronomic) Cyclophosphamide Versus Chemotherapy Alone in Patients With Non-Small Cell Lung Adenocarcinoma After Failure of Two or Three Previous Treatment Regimens for Advanced Disease

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Viagenpumatucel-L
* Drug: Metronomic Cyclophosphamide
* Drug: Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-small cell lung adenocarcinoma At least 2 and no more than 3 prior lines of therapy for incurable or metastatic NSCLC Suitable for conventional single agent chemotherapy Disease progression at study entry Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1; PS=2 patients may be considered Central nervous system (CNS) metastases may be permitted but must be treated and neurologically stable Adequate laboratory parameters Willing and able to comply with the protocol and sign informed consent Female patients who are of childbearing potential and fertile male patients must agree to use an effective form of contraception throughout study participation Exclusion Criteria: Received systemic anticancer therapy or radiation therapy within the previous 14 days Received more than 3 lines of prior conventional therapy for advanced disease Human immunodeficiency virus (HIV), hepatitis B or C, or severe/uncontrolled infections or intercurrent illness, unrelated to the tumor, requiring active therapy Any condition requiring concurrent systemic immunosuppressive therapy Known immunodeficiency disorders Known leptomeningeal disease Other active malignancies Prior treatment with a cancer vaccine for this indication Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Viagenpumatucel-L Plus Metronomic Cyclophosphamide<br>Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. | Drug: Viagenpumatucel-L<br>* Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig<br>* Other names: HS-110;Drug: Metronomic Cyclophosphamide<br>* One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks<br>|
| Active Comparator: Chemotherapy Alone<br>Patients will be treated with a physician's choice regimen until progression. | Drug: Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed)<br>* Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival (OS) calculated as the duration of survival from the date of randomization to the date of death from any cause, or was censored on the date the patient was last known to be alive. Survival time was calculated from the randomization date up to the date of death,or censored on the date that the patient was last known to be alive (last available visit date) utilizing Kaplan-Meier Estimate of Overall Survival Ending Events | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Adverse Events: Number of Participants With Treatment-Emergent Adverse Events (TEAE) | Evaluate the safety of the combination of viagenpumatucel-L and low-dose cyclophosphamide by frequency of Treatment-Emergent Adverse Events | Up to 3 years | 
| Disease Control Rate (DCR) | Evaluate overall immune-related DCR (irDCR) and also DCR by Response Evaluation Criteria in Solid Tumors (RECIST) (complete response, partial response, and stable disease) | Up to 3 years | 
| 6-Month Disease Control Rate (6mDCR) | Evaluate 6-month immune-related DCR (6m-irDCR) and also 6mDCR by RECIST (complete response, partial response, and stable disease at 6 months following randomization) | 6 months | 
| Overall Response Rate (ORR) | Evaluate immune-related ORR (irORR) and also ORR by RECIST (complete response and partial response) | Up to 3 years | 
| Progression-Free Survival (PFS) | Evaluate immune-related PFS (irPFS) and PFS by RECIST (Response Evaluation Criteria for Solid Tumors) | Up to 3 years | 
| Time to Progression (TTP) | Evaluate immune-related TTP (irTTP) and also TTP (Time to Progression) by RECIST | Up to 3 years | 
| Survival at 6 Months | Evaluate the proportion of patients who are alive at 6 months following randomization | 6 months | 
| Survival at 12 Months | Evaluate the proportion of patients who are alive at 12 months following randomization | 12 months | 
| Immune Response | Characterize the peripheral blood immunologic response via intracellular cytokine staining (ICS) by flow cytometry and/or enzyme-linked immunosorbent spot (ELISPOT) on cluster of differentiation 8 positive (CD8+) cells following vaccination | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung, cancer, gp96, vaccine, immunotherapy, Heat Biologics, cyclophosphamide, vinorelbine, erlotinib, gemcitabine, paclitaxel, docetaxel, pemetrexed