CD40 Agonist, Flt3 Ligand, and Chemotherapy in HER2 Negative Breast Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-99
SponsorUniversity of Texas Southwestern Medical Center
About this trial
This research study is being done to find out if the immunotherapy drugs called CDX-301 and CDX-1140 in combination with the standard chemotherapy treatment pegylated liposomal doxorubicin (PLD, Doxil) are safe and effective at controlling the cancer in patients with metastatic triple Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer, and to determine a safe dose and treatment schedule of the three drugs. This research study will also test how your immune system responds to these treatments alone and in combination.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Unresectable Stage III or Stage IV HER2 negative breast cancer (either triple negative or hormone receptor positive)
Triple negative breast cancer for this study is defined as estrogen receptor <10%, progesterone receptor <10% by immunohistochemistry, and HER2- negative by Herceptest (0 or 1+) or not amplified by in situ hybridization as per routine clinical testing.
Hormone receptor positive breast cancer for this study is defined as either estrogen receptor ≥10% or progesterone receptor ≥10% by immunohistochemistry, and HER2- negative by Herceptest (0 or 1+) or not amplified by in situ hybridization as per routine clinical testing.
Age 18 years or older
Disqualifiers
Among any patients enrolled in the first line treatment setting, tumors should not be PD-L1+ by 22C3 assays or eligible for FDA approved standard of care chemotherapy and anti-PD-1/PD-L1 combination therapy as alternative to this clinical trial. This does not apply if patients have previously received PD-1 or PD-L1 blockade as part of neoadjuvant or adjuvant therapy regimen.
History of severe hypersensitivity reactions to mAbs.
Prior treatment with any anti-CD40 antibody or rhuFlt3L product.
Treatment with anthracycline in the metastatic setting.
Trial design
Design model
Parallel
Treatments tested in this trial
PLD Chemotherapy
DrugPLD chemotherapy will be administered 40 mg/m2 as intravenous injection once per cycle.
CDX-1140
DrugCDX-1140 will be administered 1.5mg/kg as intravenous injection once per cycle.
CDX-301
DrugCDX-301 will be administered 75µg/kg as subcutaneous injection daily x 5 doses per cycle for 2 cycles.
Treatment groups
30 Participants
are divided into 2 treatment groupsGroup A: Cohort AExperimental treatment 3 interventions
Group B: Cohort CExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Safety (tolerability) of the drug combination of CDX-1140, CDX-301 and PLD as measured by the number of participants with Dose Limiting Toxicity (DLT)
DLTs are defined as toxicities that meet pre-defined severity criteria including serious Hematologic/Non-Hematologic adverse events (AEs) and AEs at Grade 3 or above; Any ≥ grade 2 eye pain or reduction of visual acuity that does not improved to ≤ grade 1 severity within 2 weeks of initiation of topical therapy or requires systemic treatment. Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
Time frame
Baseline up to 12 monthsSecondary outcomes
1
Anti-tumor immune response by on-treatment CD8 T cell infiltrate
Anti-tumor immune response will be measured by on-treatment CD8 T cell infiltrate in cells/mm\^2.
Time frame
After Cycle 1 (~4 weeks)2
Change in CD8 T cell infiltrate
Change in CD8 T cell infiltrate will be measured in cells/mm\^2 after cycle 1 compared to baseline.
Time frame
Baseline, After Cycle 1 (~4 weeks)3
Median Progression Free Survival by RECIST v1.1 with administration of CDX-1140, CDX-301, and PLD chemotherapy.
Median Progression Free Survival measured by RECIST v1.1, defined as the time from randomization to the time of radiographic progression or death from any cause during the study, whichever occurs first.
Time frame
Baseline until date of first observed disease progression or death, assessed up to12 months4
Overall Response Rate(ORR) by RECIST v1.1 with administration of CDX-1140, CDX-301, and PLD chemotherapy.
Best ORR by RECIST v1.1 defined as the proportion of patients with an objective tumor response (either partial response \[PR\] or complete response \[CR\] per investigator.
Time frame
Baseline until date of first observed objective tumor response assessed up to12 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Texas Southwestern Medical Center
Lead sponsor
Celldex Therapeutics
Collaborator
Gateway for Cancer Research
Collaborator
National Cancer Institute (NCI)
Collaborator
Source ClinicalTrials.gov