CD40 Agonist, Flt3 Ligand, and Chemotherapy in HER2 Negative Breast Cancer

Required: HER2 (ERBB2) wild-type (Herceptest 0 or 1+ or not amplified by in situ hybridization)

HER2- negative by Herceptest (0 or 1+) or not amplified by in situ hybridization as per routine clinical testing

Required: ESR1 low expression (<10% by immunohistochemistry)

Triple negative breast cancer for this study is defined as estrogen receptor <10%, progesterone receptor <10% by immunohistochemistry, and HER2- negative

Required: PR (PGR) low expression (<10% by immunohistochemistry)

Triple negative breast cancer for this study is defined as estrogen receptor <10%, progesterone receptor <10% by immunohistochemistry, and HER2- negative

Required: ESR1 high expression (≥10% by immunohistochemistry)

Hormone receptor positive breast cancer for this study is defined as either estrogen receptor ≥10% or progesterone receptor ≥10% by immunohistochemistry, and HER2- negative

Required: PR (PGR) high expression (≥10% by immunohistochemistry)

Hormone receptor positive breast cancer for this study is defined as either estrogen receptor ≥10% or progesterone receptor ≥10% by immunohistochemistry, and HER2- negative

Excluded: FLT3 mutation

tumor with known Flt3 mutation/amplification

Excluded: FLT3 amplification

tumor with known Flt3 mutation/amplification

Excluded: PD-L1 (CD274) positive

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.

Must have received: CDK4/6 inhibitor — metastatic

subjects must have received prior cyclin dependent kinase inhibitor in the metastatic setting

Cannot have received: anti-CD40 antibody

Prior treatment with any anti-CD40 antibody

Cannot have received: rhuFlt3L product

Prior treatment with any...rhuFlt3L product

Cannot have received: anthracycline

Exception: prior anthracycline therapy with a cumulative doxorubicin-equivalent dose ≤ 240 mg/m2 allowed

Treatment with anthracycline in the metastatic setting. For patients with triple negative breast cancer- prior anthracycline therapy with a cumulative doxorubicin-equivalent dose greater than 240 mg/m2 [excluded].

Cannot have received: anthracycline

Prior progression while on anthracycline based therapy or within 6 months of completing neoadjuvant or adjuvant anthracycline

Cannot have received: T-cell or other cell-based therapies

Prior T-cell or other cell-based therapies within 12 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)

Cannot have received: antibody targeting T cell check point or co-stimulation pathways

Receipt of any antibody targeting T cell check point or co-stimulation pathways within 4 weeks

Cannot have received: monoclonal antibody

use of any other monoclonal based therapies within 4 weeks

Cannot have received: immunotherapy

all other immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks prior to the planned start of study treatment

Cannot have received: systemic radiation therapy

Systemic radiation therapy within 4 weeks

Cannot have received: focal radiotherapy

prior focal radiotherapy within 2 weeks

Cannot have received: radiopharmaceuticals (strontium, samarium)

radiopharmaceuticals (strontium, samarium) within 8 weeks prior to the first dose of study treatment

Cannot have received: chemotherapy

Chemotherapy or antibody drug conjugate within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned start of study treatment

Cannot have received: antibody drug conjugate

Chemotherapy or antibody drug conjugate within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned start of study treatment

Cannot have received: kinase inhibitor

Any kinase inhibitors within 2 weeks prior to the first dose of study treatment

Cannot have received: investigational drug

Use of other investigational drugs within 4 weeks or 5 half-lives (whichever is longer) prior to study treatment administration