Details

Details

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)

IRB HEAT1515

CC 15-1567

Hospital Main Campus

Phase Phase 1, Phase 2

Disease Lung - NSCLC (Non-small cell lung cancer)

Drug Viagenpumatucel-L

Description

Description

Primary Objectives
  • Phase 1b: To characterize the safety and tolerability of vaccination with viagenpumatucel-L in combination with multiple immune modulating strategies in patients with NSCLC.
  • Phase 2: To evaluate objective response rate (ORR) by RECIST.
Secondary Objectives
  • Phase 1b:
    • To evaluate ORR by RECIST.
    • To characterize the peripheral blood immunologic response via intracellular cytokine staining (ICS) on IFNγ-positive CD8 + cells following vaccination.
    • To evaluate overall survival (OS).
    • To evaluate progression-free survival (PFS).
  • Phase 2:
    • To evaluate the safety and tolerability of viagenpumatucel-L in combination with other immune modulating strategies.
    • To characterize the peripheral blood immunologic response via ICS on IFNγ-positive CD8 + cells following vaccination.
    • To evaluate OS.
    • To evaluate PFS.
Exploratory Objectives
  • To evaluate exploratory endpoints, for both Phase 1 and 2, which may include:
    • Characterization of T-cell receptor (TCR) repertoire.
    • Peripheral blood immunological response by flow cytometry and/or ELISPOT analysis.
    • Total peripheral blood mononuclear cell (PBMC) counts by flow cytometry, including lymphocyte subsets.
    • Evaluation of archival and fresh biopsy tissue for shared tumor antigen expression, expression of MHC class I, presence of tumor-infiltrating lymphocytes (TILs), correlation of pre- and post-treatment TIL levels with clinical outcomes, and expression of immunosuppressive molecules.
    • To evaluate disease control rate (DCR) by RECIST at the end of the 18 week treatment period.
    • To evaluate OS at 6 months and 12 months.
Inclusion Criteria

Inclusion Criteria

  1. Histologically or cytologically confirmed non-small cell lung adenocarcinoma. Patients with mixed histology are not eligible.
  2. At least one site of measurable disease as defined by RECIST 1.1 by CT scan or MRI.
  3. Received at least one prior line of therapy for incurable or metastatic NSCLC, including cytotoxic chemotherapy, molecularly-targeted agents, or immunotherapy.
  4. Life expectancy ≥18 weeks.
  5. Documented disease progression at study entry.
  6. Age ≥ 18 years.
  7. ECOG performance status (PS) ≤1; ECOG PS=2 patients may be considered after discussion with the Medical Monitor.
  8. CNS metastases may be permitted after discussion with the Medical Monitor but must be treated and radiographically and neurologically stable: Patients with CNS metastases may be eligible after discussion with the medical monitor, provided that the brain lesions have been previously irradiated, including whole brain radiation therapy or radiosurgery, completed at least four weeks prior to enrollment, and the disease is stable both neurologically and radiologically. Stable CNS metastases are defined by the return of neurological symptoms to baseline, use of no more than 10 mg of prednisone or equivalent per day, and no evidence of new or active brain lesions in the repeated scan prior to study entry.
  9. Lab parameters:
    • Albumin ≥ 2.5 mg/dL.
    • Total Bilirubin <3.0 x upper limit of normal (ULN) unless known Gilbert's syndrome.
    • Alanine transaminase (ALT) and aspartate transaminase (AST) ≤3.0 x ULN or ≤5 x ULN in the case of liver metastases.
    • Calculated or measured creatinine clearance >35 mL/minute per the Cockcroft-Gault formula.
    • Absolute neutrophil count ≥ 1,500/mm3.
    • Hemoglobin ≥ 9g/dL.
    • Platelet count ≥ 100,000/mm3.
  10. Willing and able to comply with the protocol and sign informed consent, including weekly viagenpumatucel-L injections for 18 weeks and treatment with one of the combination regimens.
  11. Female patients who are of childbearing potential and fertile male patients must agree to use an effective form of contraception (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) with their sexual partners throughout study participation. Female patients of childbearing potential must test negative for pregnancy prior to enrolling in the trial.
  12. For Arms 2, 3 and 4:
    • Willing to provide either archival or fresh biopsy sample at screening and fresh tumor biopsy at Week 10. Archival tissue used as the baseline sample must be discussed with the Sponsor and/or Medical Monitor to confirm the archival sample is representative of the patient's current disease state (e.g., recent biopsy of the current metastatic disease).
    • Suitable for treatment with nivolumab, per the package insert.
Exclusion Criteria

Exclusion Criteria

  1. Received systemic anticancer therapy within the previous 21 days.
  2. Human immunodeficiency virus (HIV), hepatitis B or C, or severe/uncontrolled infections or concurrent illness, unrelated to the tumor, requiring active therapy. Testing is not required in the absence of history.
  3. Any condition requiring concurrent systemic immunosuppressive therapy.
  4. Known immunodeficiency disorders, either primary or acquired.
  5. Known leptomeningeal disease.
  6. Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome.
  7. Pregnant or breastfeeding.
  8. Prior treatment with a cancer vaccine for this indication.
  9. Prior participation in a clinical study of viagenpumatucel-L.
  10. Administration of a live, attenuated vaccine within 30 days prior to first dose of study drug.
  11. Active, known, or suspected autoimmune disease.
  12. For Arms 2, 3, and 4:
    • Prior treatment with a checkpoint inhibitor.