Pancreatic Cancer, Cancer of the Pancreas, Pancreas Cancer
Conditions
Brief summary
The central hypothesis is that the addition of CDX-301 to CDX-1140 radically improves anti-tumor immunity in patients with pancreatic ductal adenocarcinoma.
Interventions
DRUGCDX-301
The drug will be supplied free of charge by Celldex
DRUGCDX-1140
The drug will be supplied free of charge by Celldex
PROCEDUREResearch blood draw
At screening; prior to first therapeutic dose of CDX-1140, on the day of the infusion; and at the time of surgery
Sponsors
Celldex Therapeutics
The Foundation for Barnes-Jewish Hospital
National Cancer Institute (NCI)
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Amount of Intratumoral Conventional Dendritic Cells (cDCs) | At time of surgery (estimated to be between day 8 and day 20) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CDX-1140 Monotherapy Patients randomized to the CDX-1140 monotherapy arm will receive a single IV infusion at a dose of 1.5 mg/kg, with surgery to follow 7-12 days after administration of CDX-1140. | 8 |
| CDX-1140 + CDX-301 Patients randomized to the CDX-301 + CDX-1140 arm will receive CDX-301 at 75 mcg/kg/day as a subcutaneous injection every day for 5 days (Days 1-5) with CDX-1140 IV at 1.5 mg/kg on Day 8 +/-1 day. Surgery will be 7-12 days after administration of CDX-1140. | 8 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not start treatment due to disease progression and no longer having resectable disease | 0 | 1 |
| Overall Study | Did not start treatment due to surgery needing to occur urgently | 1 | 0 |
Baseline characteristics
| Characteristic | CDX-1140 Monotherapy | Total | CDX-1140 + CDX-301 |
|---|---|---|---|
| Age, Continuous | 69 years | 65 years | 64 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 16 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 15 Participants | 8 Participants |
| Region of Enrollment United States | 8 participants | 16 participants | 8 participants |
| Sex: Female, Male Female | 2 Participants | 10 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 8 | 3 / 8 |
| other Total, other adverse events | 7 / 7 | 7 / 7 |
| serious Total, serious adverse events | 1 / 7 | 3 / 7 |
Outcome results
Primary
Amount of Intratumoral Conventional Dendritic Cells (cDCs)
Time frame: At time of surgery (estimated to be between day 8 and day 20)
Population: Participants were not included in the overall number of participants analyzed if there was insufficient tumor for additional analysis or small tumor size.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CDX-1140 Monotherapy | Amount of Intratumoral Conventional Dendritic Cells (cDCs) | 0.9615 percentage of total cells | Standard Deviation 0.3699 |
| CDX-1140 + CDX-301 | Amount of Intratumoral Conventional Dendritic Cells (cDCs) | 2.631 percentage of total cells | Standard Deviation 0.8024 |