BATs Treatment for Pancreatic Cancer, Phase Ib/II

NCT03269526 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 19236
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Locally Advanced Pancreatic Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  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.

  From the beginning of treatment (bridging chemotherapy) until no sooner than 30 days following the last study treatment

• Overall survival

  An improvement in median overall survival (OS), defined as an increase from historical data of 8.7 months to 18.0 months.

  Until subject's death or study closure (whichever occurs first) for an average of 36 months from study treatment completion

Secondary Outcomes (3)

• Cellular or humoral anti-pancreatic cancer responses

  Every 2-6 months after the last EGFR BATs infusion for as long as the response lasts -- an average of 4 months

• Clinical Efficacy

  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

• Examine tumor tissue for immune system cells, cytokines and proteins to estimate whether the type and number of immune cells correlates with clinical responses

  Tumor paraffin blocks from tissue collected prior to treatment will be batched and analyzed within 1 year of completion of study accrual

Study Arms (1)

EGFR BATs after standard of care chemo

EXPERIMENTAL

Subjects 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.

Drug: EGFR BATs after standard of care chemo

Interventions

EGFR BATs after standard of care chemo DRUG

Subjects will receive one dose of standard of care chemotherapy prior to twice weekly or weekly infusions of EGFR BATs for 4 weeks.

EGFR BATs after standard of care chemo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Expected survival ≥ 3 months
• ECOG Performance Status 0 or 1
• Left Ventricular Ejection Fraction (LVEF) ≥ 45% at rest (MUGA or Echo)
• Age ≥ 18 years at the time of consent (Written informed consent and HIPAA authorization for release of personal health information)
• Females of childbearing potential, and males, must be willing to use an effective method of contraception
• 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.
• 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

You may not qualify if:

• Known hypersensitivity to cetuximab or other EGFR antibody
• Treatment with any investigational agent within 14 days prior to first study intervention (apheresis) for protocol therapy
• 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.
• Serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to "on-study" status
• Active liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• 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.
• Active bleeding or a pathological condition that is associated with a high risk of bleeding (therapeutic anticoagulation is allowed)
• Has an active infection requiring systemic therapy
• A serious uncontrolled medical disorder that in the opinion of the Investigator may be jeopardized by the treatment with protocol therapy
• Has a known history of active TB (Bacillus Tuberculosis)
• 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.
• Has received a live vaccine within 30 days of first study procedure (apheresis).
• 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.
• 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

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Related Publications (2)

• Lum LG, Thakur A, Al-Kadhimi Z, Colvin GA, Cummings FJ, Legare RD, Dizon DS, Kouttab N, Maizel A, Colaiace W, Liu Q, Rathore R. Targeted T-cell Therapy in Stage IV Breast Cancer: A Phase I Clinical Trial. Clin Cancer Res. 2015 May 15;21(10):2305-14. doi: 10.1158/1078-0432.CCR-14-2280. Epub 2015 Feb 16.

  PMID: 25688159 BACKGROUND

• Vaishampayan U, Thakur A, Rathore R, Kouttab N, Lum LG. Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients. Prostate Cancer. 2015;2015:285193. doi: 10.1155/2015/285193. Epub 2015 Feb 23.

  PMID: 25802762 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Tri Le, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Standard of care chemotherapy followed by Anti-CD3 x anti-EGFR-Bispecific Antibody Armed Activated T-cells

Study Record Dates

• First Submitted: August 11, 2017
• First Posted: August 31, 2017
• Study Start: July 28, 2017
• Primary Completion: June 13, 2023
• Study Completion: April 28, 2026
• Last Updated: June 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)