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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 : November 12, 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 or squamous cell carcinoma 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 Drug: Pembrolizumab Drug: Pemetrexed Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
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)
Actual Study Start Date : April 15, 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Arm 5: Viagenpumatucel-L + Nivolumab
Patients will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.
Biological: Viagenpumatucel-L
Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig
Other Name: HS-110

Drug: Nivolumab
Nivolumab 240mg IV q2weeks for 18 weeks or until disease progression or unacceptable toxicity. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.
Other Name: Opdivo

Experimental: Arm 6: Viagenpumatucel-L + pembrolizumab +/- pemetrexed
Patients will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/0.5 mL for 13 weeks in combination with SOC pembrolizumab ± pemetrexed every 3 weeks. Following the 13-week priming period, HS-110 injections will be administered for boosting every 3 weeks in combination with SOC pembrolizumab ± pemetrexed until confirmed disease progression or unacceptable toxicity, whichever occurs first.
Biological: Viagenpumatucel-L
Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig
Other Name: HS-110

Drug: Pembrolizumab
The recommended dose of KEYTRUDA (pembrolizumab) is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Other Name: Keytruda

Drug: Pemetrexed
The recommended dose of ALIMTA (pemetrexed) when administered with carboplatin and pembrolizumab for the initial treatment of NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2 administered as an intravenous infusion over 10 minutes prior to carboplatin on Day 1 of each 21-day cycle for 4 cycles. Pembrolizumab should be administered prior to ALIMTA when given on the same day.
Other Name: Alimta




Primary Outcome Measures :
  1. Phase 1b: Frequency of treatment emergent adverse events (TEAEs) as assessed by CTCAE v4.03. [ Time Frame: Up to 3 years ]
    The number of TEAEs and the number and percent of patients with a given TEAE will be summarized overall and by system organ class and preferred term by treatment group. The number and percent of patients with TEAEs will be tabulated by maximum severity.

  2. Phase 2: Progression Free Survival (PFS) [ Time Frame: Up to 3 years ]
    PFS will be calculated as the time between enrollment and the date of PD, as defined by RECIST 1.1 or death, whichever occurs first.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to 1 year ]
    Defined as the number of patients achieving a best overall response of complete response (CR/iCR) or partial response (PR/iPR) by RECIST 1.1 and iRECIST.

  2. Overall survival (OS) [ Time Frame: Up to 3 years ]
    OS will be calculated as the duration of survival from the date of first HS-110 dosing into the study to the date of death from any cause or will be censored on the date the patient was last known to be alive. Also evaluated at 6 and 12 months.

  3. Immune Progression-Free survival (iPFS) [ Time Frame: Up to 3 years ]
    calculated as the time between the date of first dose of HS-110 and the date of iCPD, as defined by iRECIST or death, whichever occurs first.

  4. Duration of response (DOR) [ Time Frame: Up to 1 year ]
    Calculated from the time of first response (CR or PR) until radiographic PD by RECIST 1.1

  5. Disease control rate (DCR) [ Time Frame: Up to 1 year ]
    Defined as the proportion of patients whose best overall response is PR, CR, or SD, as defined by RECIST 1.1

  6. Durable Response Rate (DRR) [ Time Frame: Up to 1 year ]
    Evaluated at 6 and 12 months. Defined as the percentage of responders with durable responses lasting at least 6 and 12 months from time of initial response by RECIST 1.1.

  7. Frequency of treatment emergent adverse events (TEAEs) as assessed by CTCAE v4.03. [ Time Frame: Up to 3 years ]
    The number of TEAEs and the number and percent of patients with a given TEAE will be summarized overall and by system organ class and preferred term by treatment group. The number and percent of patients with TEAEs will be tabulated by maximum severity.


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

  2. 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.

  3. Evaluation of peripheral blood Tumor Mutation Burden (TMB) [ Time Frame: Up to 3 years ]
    To measure the number of mutations within the tumor genome and correlation of TMB levels with clinical outcomes.

  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, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Non-small cell lung adenocarcinoma or squamous cell carcimona
  • At least one site of measurable disease by RECIST 1.1
  • Arm 5: 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 4 months of treatment) --OR--
  • Arm 6: Received front line immunotherapy (with or without chemotherapy) for incurable or metastatic NSCLC and did not progress clinically or radiographically per RECIST 1.1 at first imaging assessment, and will begin maintenance immunotherapy with standard of care pembrolizumab ± pemetrexed.
  • Life expectancy ≥18 weeks
  • Arm 5: Disease progression at study entry --OR--
  • Arm 6: Documented Stable Disease, Partial Response, Complete Response (SD/PR/CR) per RECIST 1.1 after a minimum of 9 to 12 weeks of front line immunotherapy (with or without chemotherapy).
  • 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 fresh tumor biopsy at Week 10 when feasible.
  • Arm 5: Suitable for treatment with nivolumab per package insert --OR--
  • Arm 6: Suitable for front line maintenance treatment with pembrolizumab ± pemetrexed per the current approved package inserts.

EXCLUSION CRITERIA:

  • Arm 5: Received systemic anticancer therapy within 21 days prior to first dose of study drug
  • 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 participation in a clinical study of viagenpumatucel-L (HS-110)
  • 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 immunotherapy (clinical or radiographic progression after 12 weeks or less of immunotherapy).

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: Lalaine Nguyen 760-539-7388 Lnguyen@heatbio.com
Contact: Clinical team Clinical@heatbio.com

  Show 22 Study Locations
Sponsors and Collaborators
Heat Biologics
Investigators
Principal Investigator: Daniel Morgensztern, MD 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: November 12, 2018
Last Verified: November 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
Pembrolizumab
Nivolumab
Pemetrexed
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors