cf33-hnis-antipdl1 for the treatment of metastatic triple negative breast cancer

Conditions: Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Triple-Negative Breast Carcinoma; Prognostic Stage IV Breast Cancer AJCC v8

Summary: this phase i trial tests the safety, side effects, and best dose of cf33-hnis-antipdl1 in treating patients with triple negative breast cancer that has spread to other places in the body (metastatic). cf33-hnis-antipdl1 is an oncolytic virus. this is a virus that is designed to infect tumor cells and break them down.

primary objective: i. to determine the safety and tolerability of a novel chimeric oncolytic orthopoxvirus, oncolytic virus cf33-expressing hnis/anti-pd-l1 antibody (cf33-hnis-antipdl1), by the evaluation of toxicities including: type, frequency, severity, attribution, time course, reversibility and duration according to common terminology criteria for adverse events (ctcae) 5.0 criteria. secondary objectives: i. to determine the optimal biologic dose (obd) (defined as a safe dose that induces an immune response in tumors \[increase checkpoint target pd-l1 by at least 5% and/or increase t cell infiltration by at least 10%\]) and the recommended phase ii dose (rp2d) for future expansion trial. ii. to determine tumor response rates by response evaluation criteria in solid tumors (recist) version (v)1.1 (primary) and immune-modified (i)recist (secondary). iii. to document possible therapeutic efficacy and evaluate progression-free survival, overall survival and response. exploratory objective: i. to determine the immune and genomic profiles of tumors before and after cf33-hnis-antipdl1 therapy. outline: this is a dose-escalation study. patients receive cf33-hnis-antipdl1 intratumorally (it) on days 1 and 15. treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. after completion of study treatment, patients are followed up at 30 days, then every 3 months for 1 year.

Eligibility criteria:
inclusion criteria: * documented informed consent of the participant and/or legally authorized representative * assent, when appropriate, will be obtained per institutional guidelines * agreement to research biopsies on study, once during study and end of study, exceptions may be granted with study principal investigator (pi) approval * \>= 18 years * eastern cooperative oncology group (ecog) =\< 2 * histologically confirmed metastatic triple negative breast cancer. triple negative status will be defined as estrogen receptor (er) and progesterone receptor (pr) =\< 10% by immunohistochemistry (ihc) and her2 negative, per american society of clinical oncology/college of american pathologists (asco/cap) guidelines * measurable disease by recist 1.1 * patients must have progressed on or been intolerant of at least 2 prior lines of therapy for advanced/metastatic disease. patients that qualify for immunotherapy and/or parp inhibitors must have progressed on or been intolerant of these agents * fully recovered from the acute toxic effects (except alopecia) to =\< grade 2 to prior anti-cancer therapy * must have a superficial tumor (cutaneous, subcutaneous), breast lesion or nodal metastases amenable to safe repeated intratumoral injections per treating physician and interventional radiologist review * absolute neutrophil count (anc) \>= 1,500/mm\^3 * note: growth factor is not permitted within 14 days of anc assessment unless cytopenia is secondary to disease involvement * platelets \>= 100,000/mm\^3 * note: platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement * total bilirubin =\< 1.5 x upper limit of normal (uln) * aspartate aminotransferase (ast) =\< 2.5 x uln * if liver metastases are present: ast =\< 5 x uln * alanine aminotransferase (alt) =\< 2.5 x uln * if liver metastases are present: alt =\< 5 x uln * serum creatinine =\ = 50 ml/min per 24 hour urine test or the cockcroft-gault formula * prothrombin (pt) =\< 1.5 x uln * activated partial thromboplastin time (aptt) =\< 1.5 x uln * women of childbearing potential (wocbp): negative serum pregnancy test * agreement by females and males of childbearing potential\* and their partners to use an effective method of birth control (defined as a hormonal or barrier method) or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy * childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only) exclusion criteria: * chemotherapy, biological therapy, immunotherapy or investigational therapy within 14 days prior to day 1 of protocol therapy * major surgery or radiation therapy within 28 days of study therapy * has received a vaccination within 30 days of first study injection * history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent * clinically significant uncontrolled illness * active infection requiring antibiotics * known history of immunodeficiency virus (hiv) * patients with a known history of hepatitis b or hepatitis c infection who have active disease as evidenced by hepatitis (hep) b surface antigen status or hep c polymerase chain reaction (pcr) status obtained within 14 days of cycle 1, day 1 * another malignancy within 3 years, except non-melanomatous skin cancer * females only: pregnant or breastfeeding * patients may not have clinically unstable brain metastases. patients may be enrolled with a history of treated brain metastases that are clinically stable for \>= 4 weeks prior to start of study treatment * any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures * prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)