Clinical Trials /

BATs Treatment for Pancreatic Cancer, Phase Ib/II

NCT03269526

Description:

This protocol will confirm toxicities and estimate the clinical efficacy of combining anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed activated T cells (EGFR BATs) given to patients with locally advanced or metastatic pancreatic cancer who have received at least one dose of first line chemotherapy and may have responding, stable or progressive disease. Phase Ib will confirm a safe dose of 8 infusions, given twice weekly, of EGFR-BATs in 3 to 6 subjects. The phase II portion of the trial will test the clinical efficacy of this dose in 22 patients (including those in Phase Ib).

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: BATs Treatment for Pancreatic Cancer, Phase Ib/II
  • Official Title: Phase Ib/II Treatment of Advanced Pancreatic Cancer With Anti-CD3 x Anti-EGFR-Bispecific Antibody Armed Activated T-Cells (BATs)

Clinical Trial IDs

  • ORG STUDY ID: 19236
  • NCT ID: NCT03269526

Conditions

  • Locally Advanced Pancreatic Adenocarcinoma
  • Metastatic Pancreatic Adenocarcinoma

Interventions

DrugSynonymsArms
EGFR BATs after standard of care chemoEGFR BATs after standard of care chemo

Purpose

This protocol will confirm toxicities and estimate the clinical efficacy of combining anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed activated T cells (EGFR BATs) given to patients with locally advanced or metastatic pancreatic cancer who have received at least one dose of first line chemotherapy and may have responding, stable or progressive disease. Phase Ib will confirm a safe dose of 8 infusions, given twice weekly, of EGFR-BATs in 3 to 6 subjects. The phase II portion of the trial will test the clinical efficacy of this dose in 22 patients (including those in Phase Ib).

Detailed Description

      Once subjects are determined eligible, white blood cells (lymphocytes) are collected via
      leukapheresis procedure at approximately 3 to 4 weeks prior to first EGFR-BATs infusion. The
      white blood cells, specifically T cells, are then mixed with two proteins - OKT3 and IL-2
      which activates the cells to multiply. After approximately 14 days in culture, the activated
      T cells are coated with the OKT3 and cetuximab to produce bispecific antibody armed T cells
      (BATs). Cells are then frozen and stored until scheduled to be infused.

      Within one to two weeks prior to infusion of the study treatment, subjects will receive one
      dose of chemotherapy. The choice of chemotherapy agent(s) is at the discretion of the
      treating physician.

      At approximately 4 weeks following leukapheresis procedure, twice weekly or weekly infusions
      of the BATs cells will take place (twice weekly for participants enrolled before DATE and
      weekly for participants enrolled after DATE). A total of eight twice weekly infusions or four
      weekly infusions will be given over a four week period. Please note that the weekly dose for
      both groups of participants is the same; participants that received twice weekly dosing
      received half of the weekly dose at each infusion.

      Follow-up appointment schedule will include clinic visits at 1 to 2 weeks, 4 to 5 weeks, 2
      months, 4 months and 6 months following the last infusion of BATs cells.
    

Trial Arms

NameTypeDescriptionInterventions
EGFR BATs after standard of care chemoExperimentalSubjects will undergo apheresis to collect peripheral blood mononuclear cells. Cells will be cultured for up to 2 weeks before activated T-cells will be harvested, armed with EGFR Biarmed activated T-cells, washed to remove unbound EGFRBi, and cryopreserved. Subjects will then receive one dose of standard of care chemotherapy prior to receiving EGFR BATs.
  • EGFR BATs after standard of care chemo

Eligibility Criteria

        Inclusion Criteria:

          1. Histological or cytological proof of pancreatic adenocarcinoma. Must have locally
             advanced or metastatic pancreatic cancer and received at least one dose of
             chemotherapy (any treatment line) and may have responding, stable or progressive
             disease

          2. Expected survival ≥ 3 months

          3. ECOG Performance Status 0 or 1

          4. Left Ventricular Ejection Fraction (LVEF) ≥ 45% at rest (MUGA or Echo)

          5. Age ≥ 18 years at the time of consent (Written informed consent and HIPAA
             authorization for release of personal health information)

          6. Females of childbearing potential, and males, must be willing to use an effective
             method of contraception

          7. Females of childbearing potential must have a negative pregnancy test within 10 days
             prior to "on study" status. If a urine or serum test is positive or cannot be
             confirmed as negative, the other (urine or serum pregnancy test, whichever was not
             performed first) will be required.

          8. Demonstrate adequate hepatic, renal, and bone marrow function as defined below; all
             hematological, renal, and hepatic screening labs should be performed within 10 days
             prior to "on study" status (alpha gal testing must be within the regular screening
             period).

               -  Absolute lymphocyte count ≥ 400/mm3

               -  Absolute neutrophil count (ANC) ≥ 1,000/mm3

               -  Platelets ≥ 75,000/mm3

               -  Hemoglobin ≥ 8 g/dL

               -  Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be
                  used in place of creatinine or CrCl) < 2.0 mg/dl OR ≥50 ml/mm

               -  Serum total bilirubin ≤ 2 mg/dl (biliary stent is allowed)

               -  AST (SGOT) and ALT (SGPT) < 5.0 times normal

               -  Alpha 1,3 Galactose IgE ("alpha gal") < 0.35 IU/ml or "negative"

        Exclusion Criteria:

          1. Known hypersensitivity to cetuximab or other EGFR antibody

          2. Treatment with any investigational agent within 14 days prior to first study
             intervention (apheresis) for protocol therapy

          3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             or any other form of immunosuppressive therapy within 7 days prior to first study
             intervention (apheresis). Replacement therapy (eg., thyroxine, insulin, or physiologic
             corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
             not considered a form of systemic treatment.

          4. Serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy
             or significant traumatic injury within 28 days prior to "on-study" status

          5. Active liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
             hepatitis

          6. Is HIV positive or has evidence of active Hepatitis C virus or active Hepatitis B
             virus. If initial Hepatitis C test shows a positive result, the patient should have a
             Hepatitis viral load test to confirm. If initial HIV or Hepatitis B virus testing
             shows a positive result, no further testing will be done.

          7. Active bleeding or a pathological condition that is associated with a high risk of
             bleeding (therapeutic anticoagulation is allowed)

          8. Has an active infection requiring systemic therapy

          9. A serious uncontrolled medical disorder that in the opinion of the Investigator may be
             jeopardized by the treatment with protocol therapy

         10. Has a known history of active TB (Bacillus Tuberculosis)

         11. Has had prior chemotherapy, radiation, hormonal, monoclonal antibody (mAb) or targeted
             small molecule therapy, within 2 weeks prior to the first study procedure (apheresis).
             Subjects who have not recovered to <Grade 3 from an adverse event due to a previously
             administered agent are not eligible.

         12. Has received a live vaccine within 30 days of first study procedure (apheresis).

         13. History of a recent myocardial infarction (within one year), a past myocardial
             infarction (more than one year ago) along with current coronary symptoms requiring
             medications.

         14. Has history of another malignancy within the past 5 years. Exceptions include

               -  basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has
                  undergone potentially curative therapy

               -  in situ cervical cancer.

         15. Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

         16. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

         17. Females must not be breastfeeding

         18. Pt may be excluded if, in the opinion of the PI and investigator team, the pt is not
             capable of being compliant
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:From the beginning of treatment (bridging chemotherapy) until no sooner than 30 days following the last study treatment
Safety Issue:
Description:Safety will be assessed by incidence and severity of adverse events, changes in laboratory findings, physical examinations, vital signs, and the number of dose limiting toxicities and other discontinuations due to adverse events.

Secondary Outcome Measures

Measure:Cellular or humoral anti-pancreatic cancer responses
Time Frame:Every 2-6 months after the last EGFR BATs infusion for as long as the response lasts -- an average of 4 months
Safety Issue:
Description:These will be measured in peripheral blood mononuclear cells
Measure:Clinical Efficacy
Time Frame:Imaging will be performed prior to treatment, 2 months after the last BATs infusion, then according to standard of care for an average of 12 months
Safety Issue:
Description:Progression-free survival, measured by immune-related response criteria (irRC)
Measure:Examine tumor tissue for immune system cells, cytokines and proteins to estimate whether the type and number of immune cells correlates with clinical responses
Time Frame:Tumor paraffin blocks from tissue collected prior to treatment will be batched and analyzed within 1 year of completion of study accrual
Safety Issue:
Description:These immune system cells, cytokines and proteins include CD3, CD4, CD8, PD1/PDL1, monocytes subpopulations, MDSCs, and cytoplasmic IFN-y, tumor infiltrating lymphocytes, and IL-10. This will be measured using immunohistochemical staining to quantitate type and number of immune system cells, cytokines, and proteins to estimate whether the type and number correlate with clinical responses.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Virginia

Trial Keywords

  • Pancreatic Cancer
  • Pancreatic Adenocarcinoma
  • Adoptive cell therapy
  • Armed activated T-cells
  • Bispecific antibody
  • Immunotherapy

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