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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02439450
Recruitment Status : Completed
First Posted : May 8, 2015
Last Update Posted : November 14, 2022
Sponsor:
Information provided by (Responsible Party):
Heat Biologics

Tracking Information
First Submitted Date  ICMJE May 4, 2015
First Posted Date  ICMJE May 8, 2015
Last Update Posted Date November 14, 2022
Actual Study Start Date  ICMJE April 15, 2015
Actual Primary Completion Date May 3, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 6, 2019)
  • 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.
  • Phase 2, Arm 5: 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. Analysis will be conducted on the ITT population.
  • Phase 2, Arm 6: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 6, 2015)
Safety and Tolerability by physical and laboratory examinations [ Time Frame: Up to 3 years ]
Evaluate the safety of each viagenpumatucel-L combination regimen
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2019)
  • Objective Response Rate (ORR) [ Time Frame: Up to 1 year ]
    Defined as the proportion of patients achieving a best overall response of complete response (CR) or partial response (PR) by RECIST 1.1. Analysis will be conducted on the Safety population.
  • 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.
  • Progression-Free survival (PFS) [ Time Frame: Up to 3 years ]
    Calculated as the time between the date of first dose of HS-110 and the date of PD, as defined by RECIST 1.1 or death, whichever occurs first. Also evaluated at 6 and 12 months.
  • Duration of response (DOR) [ Time Frame: Up to 1 year ]
    Calculated from the time of first confirmed response (CR or PR) until radiographic PD by RECIST 1.1
  • 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
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2015)
  • Immune Response by intracellular cytokine staining (ICS) by flow cytometry or enzyme-linked immunosorbent spot (ELISPOT) [ Time Frame: Up to 3 years ]
    Characterize the peripheral blood immunologic response on cluster of differentiation 8 positive (CD8+) cells following vaccination
  • Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]
    Evaluate the immune-related ORR (complete response and partial response)
  • Overall Survival (OS) [ Time Frame: Up to 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: May 6, 2015)
  • Tumor antigen expression by immunohistochemistry (IHC) in biopsies or archival tissue [ Time Frame: Pre-treatment ]
  • Tumor-infiltrating lymphocytes by IHC in biopsies [ Time Frame: Nine weeks after first dose of vaccine ]
  • Disease Control Rate (DCR) [ Time Frame: Up to 3 years ]
    Evaluate the immune-related DCR (complete response, partial response, or stable disease)
  • 18-week DCR [ Time Frame: After 18 weeks of treatment ]
    Evaluate the DCR (immune-related and by Response Criteria for Solid Tumors (RECIST)) at the end of the 18 week treatment period
  • 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
 
Descriptive Information
Brief Title  ICMJE A Study of Combination Therapies With Viagenpumatucel-L (HS-110) in Patients With Non-Small Cell Lung Cancer
Official Title  ICMJE 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)
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.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Biological: Viagenpumatucel-L
    • Drug: Nivolumab
  • Experimental: Arm 6: Viagenpumatucel-L + pembrolizumab +/- pemetrexed
    HS-110 dosing to be initiated at/before the start of the 3rd maintenance treatment cycle, or within 19 weeks of front-line pembrolizumab monotherapy. 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.
    Interventions:
    • Biological: Viagenpumatucel-L
    • Drug: Pembrolizumab
    • Drug: Pemetrexed
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 6, 2019)
121
Original Estimated Enrollment  ICMJE
 (submitted: May 6, 2015)
27
Actual Study Completion Date  ICMJE November 4, 2022
Actual Primary Completion Date May 3, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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, but no more than three prior lines of therapy, for incurable (i.e. unresectable) or metastatic NSCLC. Up to one prior line of FDA-approved 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 the most recent 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02439450
Other Study ID Numbers  ICMJE HS110-102
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Heat Biologics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Heat Biologics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Daniel Morgensztern, MD Washington University School of Medicine in St. Louis
PRS Account Heat Biologics
Verification Date October 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP