Celldex decision

The central hypothesis is that the addition of CDX-301 to CDX-1140 radically improves anti-tumor immunity in patients with pancreatic ductal adenocarcinoma.

Inclusion Criteria:

• Histologically or cytologically confirmed surgically resectable pancreatic ductal adenocarcinoma, but not adenosquamous/squamous pancreas cancers (as determined by operating surgeon or tumor board). Patients who have previously received chemotherapy for his/her pancreas cancer within the past 6 months and who are now deemed resectable are also eligible for this trial.

• At least 18 years of age.

• ECOG performance status ≤ 1

• Normal bone marrow and organ function as defined below:

  • Absolute neutrophil count ≥ 1,500 /cumm
  • Platelets ≥ 100,000 /cumm
  • Hemoglobin ≥ 9.0 g/dL
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
  • Creatinine clearance ≤ 1.5 x IULN or glomerular filtration rate of ≥ 60 mL/min
  • INR ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
  • aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
  • Albumin ≥ 3.0mg/dL

• The effects of CDX-301 and CDX-1140 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 3 months after the last dose of either study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study or for 3 months after the last dose of either study drug, she must inform her treating physician immediately.

• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Immune deficiencies such as HIV.
• A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
• Currently receiving any other investigational agents or has received any other investigational agents within 4 weeks or 5 half-lives of the planned first dose of study treatment.
• Receipt of chemotherapy within 2 weeks of planned first dose of study treatment.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to CDX-301 or CDX-1140 or other agents used in the study.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (for > 1 month of 10 mg prednisone daily, or equivalent) or any other form of immunosuppressive therapy not routinely associated with chemotherapeutic regimen.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, immunosuppression, autoimmune conditions, or underlying pulmonary disease.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, immunosuppression, autoimmune conditions, or underlying pulmonary disease.
• Has an autoimmune disease requiring systemic treatment within 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.
• Known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected).
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has a known history of active TB (bacillus tuberculosis).
• Major surgery within 28 days prior to the first study treatment.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
• History of bone marrow or solid organ transplant.
• Patients with a history of myocardial infarction, cerebral vascular accident, thrombosis or pulmonary embolus within 12 months prior to the first dose of study treatment are excluded from this study.
• Patients with known mutations/amplifications in Flt3

Adverse events were collected from start of treatment through time of surgery (or 60 days after end of treatment if surgery doesn't take place).

If patients did not start treatment with CDX-1140 monotherapy or CDX-1140 + CDX-301 treatment then adverse events were not collected. There was one participant in each arm who did not start treatment, therefore, adverse events were not collected on those two patients.