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

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ClinicalTrials.gov Identifier: NCT02439450
Recruitment Status : Recruiting
First Posted : May 8, 2015
Last Update Posted : February 2, 2018
Sponsor:
Information provided by (Responsible Party):
Heat Biologics

Brief Summary:
This study will test whether vaccination with viagenpumatucel-L combined with strategies to modulate the immune response is safe for patients with non-small cell lung adenocarcinoma who have failed at least one prior line of therapy for incurable or metastatic disease. These methods collectively use the body's immune system to target the patient's own tumor. Immunosuppression hinders that response, and may develop in NSCLC patients in a variety of ways, such as activation of checkpoint pathways in the tumor microenvironment. Drugs that disrupt checkpoint molecule signaling like anti-PD-1 monoclonal antibodies nivolumab, may release this brake on the immune system. Tumor expression of PD-L1 plays an important role in patient response to checkpoint inhibitors; in general, clinical response to checkpoint inhibitors requires tumor expression of PD-L1 and presence of Tumor Infiltrating Lymphocytes (TIL). Combining viagenpumatucel-L with anti-PD-1 agents may enhance the vaccine's anti-tumor activity while prolonging or increasing the efficacy of the checkpoint inhibitor.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Biological: Viagenpumatucel-L Drug: Nivolumab Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of Viagenpumatucel-L (HS-110) in Combination With Multiple Treatment Regimens in Patients With Non-Small Cell Lung Cancer (The "DURGA" Trial)
Study Start Date : April 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Nivolumab
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Viagenpumatucel-L + Nivolumab
Patients will receive a combination of weekly viagenpumatucel-L (HS-110) given as injections of 1x10^7 cells and Nivolumab for 18 weeks or until treatment discontinuation.
Biological: Viagenpumatucel-L
Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig
Other Name: HS-110
Drug: Nivolumab
Patients will receive nivolumab per the package insert for the treatment of NSCLC (240mg IV q2weeks) until disease progression or unacceptable toxicity
Other Name: Opdivo



Primary Outcome Measures :
  1. Phase 1b: Frequency of treatment emergent adverse events (TEAEs)/serious adverse events (SAEs) [Safety and Tolerability] [ Time Frame: Up to 3 years ]
    Evaluate TEAEs and SAEs (includes assessment of abnormal laboratory values, ECGs, physical exams, and vital signs) by CTCAE v4.0

  2. Phase 2: Objective Response Rate (ORR) [ Time Frame: Up to 3 years ]
    Evaluate the ORR by response evaluation criteria in solid tumors (RECIST and iRECIST)


Secondary Outcome Measures :
  1. Frequency of treatment emergent adverse events (TEAEs)/serious adverse events (SAEs) [Safety and Tolerability] [ Time Frame: Up to 3 years ]
    Evaluate TEAEs and SAEs (includes assessment of abnormal laboratory values, ECGs, physical exams, and vital signs) by CTCAE v4.0

  2. To characterize the peripheral blood immunologic response (IR) [ Time Frame: Up to 3 years ]
    To be done via Enzyme-Linked ImmunoSpot (ELISPOT) analysis

  3. Overall survival (OS) [ Time Frame: Up to 1 year ]
    Evaluated at 6 and 12 months

  4. Progression-free survival (PFS) [ Time Frame: Up to 1 year ]
    Evaluated at 6 and 12 months

  5. Duration of response (DOR) [ Time Frame: Up to 1 year ]
    Evaluated at 6 and 12 months

  6. Disease control rate (DCR) [ Time Frame: Up to 1 year ]
    Evaluated at 6 and 12 months


Other Outcome Measures:
  1. Characterization of T-cell receptor (TCR) repertoire [ Time Frame: Up to 3 years ]
    Done by flow cytometry

  2. Determination of total peripheral blood mononuclear cell (PBMC) counts (including lymphocyte subsets) [ Time Frame: Up to 3 years ]
    Done by flow cytometry

  3. Evaluation of tissue biopsies (archival or fresh) [ Time Frame: Up to 3 years ]
    Evaluated for shared tumor antigen expression, major histocompatibility (MHC) class I expression, presence of tumor-infiltrating lymphocytes (TILs), level of PD-L1 expression, correlation of pre- and post-treatment TIL levels and PD-L1 expression on tumor cells with clinical outcomes, and expression of immunosuppressive molecules.

  4. Perform other exploratory analysis of peripheral blood and tumor tissue to determine immune changes and response to treatment [ Time Frame: Up to 3 years ]
    This may be conducted as new technology emerges



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Non-small cell lung adenocarcinoma or squamous cell carcimona
  • One site of measurable disease by RECIST 1.1
  • Received at least one prior line of therapy for incurable or metastatic NSCLC. Up to one prior line of checkpoint inhibitor therapy is permitted (must have received at least 6 months of treatment).
  • Life expectancy ≥18 weeks
  • Disease progression at study entry
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  • 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
  • Willing to provide archival or fresh tumor biopsy at Screening and Week 10
  • Suitable for treatment with nivolumab per package insert

Exclusion Criteria:

  • Received systemic anticancer therapy within the previous 21 days
  • Human immunodeficiency virus (HIV), hepatitis B or C, or severe/uncontrolled infections or concurrent illness, unrelated to the tumor, requiring active therapy
  • Any condition requiring concurrent systemic immunosuppressive therapy
  • Known immunodeficiency disorders, either primary or acquired
  • Known leptomeningeal disease
  • Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
  • Pregnant or breastfeeding
  • Prior treatment with a cancer vaccine for this indication
  • Prior participation in a clinical study of viagenpumatucel-L
  • Administration of a live vaccine within 30 days prior to first dose of study drug
  • Active, known or suspected autoimmune disease
  • Significant cardiovascular disease
  • Refractory to prior checkpoint inhibitor therapy (received less than 6 months of treatment)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02439450


Contacts
Contact: Hannah McKay 919-794-7915 hmckay@heatbio.com

Locations
United States, Alabama
University of Alabama - Birmingham Withdrawn
Birmingham, Alabama, United States, 35294
United States, California
UC San Diego Recruiting
La Jolla, California, United States, 92093
Contact: Conrad Tydon    858-822-0217    cltydon@ucsd.edu   
Principal Investigator: Lyudmila Bazhenova, MD         
United States, Indiana
Horizon Oncology Research Recruiting
Lafayette, Indiana, United States, 47905
Contact: Elizabeth Morris, RN    765-446-5165    emorris@horizonbioadvance.com   
Principal Investigator: Wael Harb, MD         
United States, Kentucky
Ashland-Bellefonte Cancer Center Recruiting
Ashland, Kentucky, United States, 41101
Contact: Alicia Pinson    606-388-2667    apinson@abcc.us   
Principal Investigator: Venu Konala, MD         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Allie Gordon    314-747-5543    allison.gordon@wustl.edu   
Principal Investigator: Daniel Morgensztern, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Polly Brogan    216-445-7101    broganp@ccf.org   
Principal Investigator: Vamsi Velcheti, MD         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Brenda Fisher    503-215-2614    brenda.fisher@providence.org   
Principal Investigator: Rachel Sanborn, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Pooja Patel    215-220-9700    Pooja.Patel@uphs.upenn.edu   
Principal Investigator: Roger Cohen, MD         
Sponsors and Collaborators
Heat Biologics
Investigators
Principal Investigator: Daniel Morgensztern Washington University School of Medicine in St. Louis

Responsible Party: Heat Biologics
ClinicalTrials.gov Identifier: NCT02439450     History of Changes
Other Study ID Numbers: HS110-102
First Posted: May 8, 2015    Key Record Dates
Last Update Posted: February 2, 2018
Last Verified: January 2018

Keywords provided by Heat Biologics:
lung
cancer
gp96
vaccine
immunotherapy
Heat Biologics
Nivolumab
checkpoint inhibitor

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs