We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study is currently recruiting participants.
Verified July 2017 by Heat Biologics
Sponsor:
ClinicalTrials.gov Identifier:
NCT02439450
First Posted: May 8, 2015
Last Update Posted: July 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Heat Biologics
  Purpose
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 than 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 Intervention Phase
Non-small Cell Lung Cancer Biological: Viagenpumatucel-L Drug: Nivolumab Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel 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)

Resource links provided by NLM:


Further study details as provided by Heat Biologics:

Primary Outcome Measures:
  • Phase 1b: Safety and Tolerability by physical and laboratory examinations [ Time Frame: Up to 3 years ]
    Evaluate the safety of each viagenpumatucel-L combination regimen

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


Secondary Outcome Measures:
  • Phase 1b: Objective Response Rate (ORR) [ Time Frame: Up to 3 years ]
    Evaluate the objective response rate (ORR) by response evaluation criteria in solid tumors (RECIST)

  • Phase 2: Safety and Tolerability by physical and laboratory examinations [ Time Frame: Up to 3 years ]
    Evaluate the safety of each viagenpumatucel-L combination regimen

  • Immune Response by intracellular cytokine staining (ICS) by flow cytometry [ Time Frame: Up to 3 years ]
    Characterize the peripheral blood immunologic response on cluster of differentiation 8 positive (CD8+) cells following vaccination

  • Overall Survival (OS) [ Time Frame: Up to 3 years ]
  • Progression-Free Survival (PFS) [ Time Frame: Up to 3 years ]

Other Outcome Measures:
  • Characterization of T-cell receptor (TCR) repertoire [ Time Frame: Up to 3 years ]
  • Peripheral Blood Immune Response by Flow Cytometry and/or ELISPOT Analysis [ Time Frame: Up to 3 years ]
  • Total Peripheral Blood Mononuclear Cell (PBMC) counts by Flow Cytometry including Lymphocyte Subsets [ Time Frame: Up to 3 years ]
  • Tumor antigen expression by immunohistochemistry (IHC) and presence of tumor-infiltrating lymphocytes (TILs) in biopsies or archival tissue [ Time Frame: Pre-treatment ]
  • Tumor-infiltrating lymphocytes and expression of Immunosuppressive Molecules by IHC in biopsies [ Time Frame: Nine weeks after first dose of study drug ]
  • Disease Control Rate (DCR) [ Time Frame: Up to 3 years ]
    Evaluate the DCR by response evaluation criteria in solid tumors (RECIST) (complete response, partial response or stable disease)

  • Survival at 6 months [ Time Frame: 6 months ]
    Evaluate the proportion of patients who are alive at 6 months following enrollment

  • Survival at 12 months [ Time Frame: 12 months ]
    Evaluate the proportion of patients who are alive at 12 months following enrollment


Estimated Enrollment: 100
Study Start Date: April 2015
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Viagenpumatucel-L + Nivolumab (Low TIL)
Patients with low TIL (tumor-infiltrating lymphocytes) will receive a combination of weekly viagenpumatucel-L (HS-110) given as injections of 1*10^7 cells and Nivolumab for 18 weeks or until treatment discontinuation. 9 patients will initially be enrolled (Phase 1b) with an option to expand to 30 patients based on preliminary efficacy (Phase 2).
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 (3 mg/kg as an i.v. infusion over 60 minutes every two weeks) until disease progression or unacceptable toxicity
Other Name: Opdivo
Experimental: Viagenpumatucel-L + Nivolumab (High TIL)
Patients with high TIL (tumor-infiltrating lymphocytes) will receive a combination of weekly viagenpumatucel-L (HS-110) given as injections of 1*10^7 cells and Nivolumab for 18 weeks or until treatment discontinuation. 9 patients will initially be enrolled (Phase 1b) with an option to expand to 30 patients based on preliminary efficacy (Phase 2).
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 (3 mg/kg as an i.v. infusion over 60 minutes every two weeks) until disease progression or unacceptable toxicity
Other Name: Opdivo
Experimental: Viagenpumatucel-L + Nivolumab (Rollover)
Patients will receive a combination of weekly viagenpumatucel-L (HS-110) given as injections of 1*10^7 cells and Nivolumab for 18 weeks or until treatment discontinuation. This arm allows patients who have consented but could not be assigned to Arm 2 or 3 to enroll and there is no formal limit.
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 (3 mg/kg as an i.v. infusion over 60 minutes every two weeks) until disease progression or unacceptable toxicity
Other Name: Opdivo

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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
  • One site of measureable disease by RECIST 1.1
  • Received at least one prior line of therapy for incurable or metastatic NSCLC
  • Life expectancy ≥18 weeks
  • 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
  • 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, attenuated vaccine within 30 days prior to first dose of study drug
  • Active, known or suspected autoimmune disease
  • Prior treatment of checkpoint inhibitor
  Contacts and Locations
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, Indiana
Horizon Oncology Research, Inc. Recruiting
Lafayette, Indiana, United States, 47905
Contact: Elizabeth Morris, RN    765-446-5165    emorris@horizonbioadvance.com   
Principal Investigator: Wael A Harb, MD         
United States, Kentucky
Ashland-Bellefonte Cancer Center Recruiting
Ashland, Kentucky, United States, 41101
Contact: Asheesh Jain    606-836-0202 ext 119    asheesh@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         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Natisha Muhammad    215-349-8743    Natisha.Muhammad@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
  More Information

Responsible Party: Heat Biologics
ClinicalTrials.gov Identifier: NCT02439450     History of Changes
Other Study ID Numbers: HS110-102
First Submitted: May 4, 2015
First Posted: May 8, 2015
Last Update Posted: July 19, 2017
Last Verified: July 2017

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