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

NCT02439450

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.

Related Conditions:
  • Lung Adenocarcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: HS110-102
  • NCT ID: NCT02439450

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
Viagenpumatucel-LHS-110Arm 5: Viagenpumatucel-L + Nivolumab
NivolumabOpdivoArm 5: Viagenpumatucel-L + Nivolumab
PembrolizumabKeytrudaArm 6: Viagenpumatucel-L + pembrolizumab +/- pemetrexed
PemetrexedAlimtaArm 6: Viagenpumatucel-L + pembrolizumab +/- pemetrexed

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 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.

Trial Arms

NameTypeDescriptionInterventions
Arm 5: Viagenpumatucel-L + NivolumabExperimentalPatients 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.
  • Viagenpumatucel-L
  • Nivolumab
Arm 6: Viagenpumatucel-L + pembrolizumab +/- pemetrexedExperimentalPatients 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.
  • Viagenpumatucel-L
  • Pembrolizumab
  • Pemetrexed

Eligibility 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1b: Frequency of treatment emergent adverse events (TEAEs) as assessed by CTCAE v4.03.
Time Frame:Up to 3 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to 1 year
Safety Issue:
Description: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.
Measure:Overall survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:Immune Progression-Free survival (iPFS)
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:Duration of response (DOR)
Time Frame:Up to 1 year
Safety Issue:
Description:Calculated from the time of first response (CR or PR) until radiographic PD by RECIST 1.1
Measure:Disease control rate (DCR)
Time Frame:Up to 1 year
Safety Issue:
Description:Defined as the proportion of patients whose best overall response is PR, CR, or SD, as defined by RECIST 1.1
Measure:Durable Response Rate (DRR)
Time Frame:Up to 1 year
Safety Issue:
Description: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.
Measure:Frequency of treatment emergent adverse events (TEAEs) as assessed by CTCAE v4.03.
Time Frame:Up to 3 years
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Heat Biologics

Trial Keywords

  • lung
  • cancer
  • gp96
  • vaccine
  • immunotherapy
  • Heat Biologics
  • Nivolumab
  • checkpoint inhibitor

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