Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Doxorubicin

Liposomal doxorubicin

Immunoglobulins

Flt3 ligand protein

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

PLD chemotherapy will be administered 40 mg/m2 as intravenous injection once per cycle until toxicity or progression.

CDX-1140 will be administered 1.5mg/kg as intravenous injection once per cycle until toxicity or progression for up to 24 months.

CDX-301 will be administered 75µg/kg as subcutaneous injection daily x 5 days cycles 1 and 2 only.

PLD chemotherapy will be administered 40 mg/m2 as intravenous injection once per cycle starting on cycle 2 until toxicity or progression.

CDX-1140 will be administered 1.5mg/kg as intravenous injection once per cycle until toxicity or progression for up to 24 months.

CDX-301 will be administered 75µg/kg as subcutaneous injection daily x 5 days cycles 1 and 2 only.

PLD chemotherapy will be administered 40 mg/m2 as intravenous injection once per cycle until toxicity or progression.

CDX-1140 will be administered 1.5mg/kg as intravenous injection once per cycle starting on cycle 2 until toxicity or progression for up to 24 months.

CDX-301 will be administered 75µg/kg as subcutaneous injection daily x 5 days cycles 2 and 3 only.

PLD chemotherapy will be administered 40 mg/m2 as intravenous injection once per cycle.

PLD Chemotherapy

CDX-1140 will be administered 1.5mg/kg as intravenous injection once per cycle.

CDX-1140

CDX-301 will be administered 75µg/kg as subcutaneous injection daily x 5 doses per cycle for 2 cycles.

CDX-301

Meredith Carter, MS

Nan Chen, MD

Taylor Embry

Cesar A. Santa-Maria, MD,MSCI

Denise Yardley, MD

Kelly Goddard

Joyce O'Shaughnessy, MD

Christine Terraciano

Sangeetha Reddy, MD

Virginia Kaklamani, MD,DSC

Sangeetha Reddy

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 negative breast cancer, and to determine a safe dose and treatment schedule of the three drugs. This research study will also test how these treatments improve your body's immune response against the cancer.

The immunotherapy drugs CDX-301 and CDX-1140 in combination with the standard chemotherapy treatment PLD work by kickstarting the immune response against cancer cells. CDX-301 increases the antigen presenting immune cells needed to kickstart the immune response, CDX-1140 activates these cells, and chemotherapy helps release antigens from the cancer cells to train these antigen presenting immune cells to recognize the cancer for the immune system to attack it.

Metastatic or unresectable triple negative breast cancer patients will receive this triplet combination that has been shown in preclinical studies to be more effective than the individual treatments or doublet combinations. To understand how the immunotherapies are working, some patients will receive the immunotherapy or chemotherapy only for one cycle prior to receiving the full triplet combination therapy. Ultimately, all patients will receive the triplet combination to study safety and how effective this treatment is at controlling triple negative breast cancer and improving survival outcomes.

CD40 Agonist, Flt3 Ligand, and Chemotherapy in Triple Negative Breast Cancer

Phase 1 Pilot Study With Dose Expansion of Chemotherapy in Combination With CD40 Agonist and Flt3 Ligand in Metastatic Triple Negative Breast Cancer

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

Anti-tumor immune response will be measured by on-treatment CD8 T cell infiltrate in cells/mm\^2.

Change in CD8 T cell infiltrate will be measured in cells/mm\^2 after cycle 1 compared to baseline.

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.

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.

Duration of response (DoR) defined as the time from the first occurrence of a documented objective tumor response to the time of radiographic progression (per investigator using RECIST v1.1) or death from any cause on study, whichever occurs first.

CBR defined as percentage of patients with CR, PR, or stable disease \[SD\] by RECIST v1.1 at 6 months.

Spots Global Cancer Trial Database for pld chemotherapy