Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8
Conditions
Brief 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.
Detailed description
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.
Interventions
BIOLOGICALOncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody
Given IT
Sponsors
City of Hope Medical Center
National Cancer Institute (NCI)
Imugene Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 =\< 1.5 mg/dL or creatinine clearance of \>= 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | Up to 30 days | Toxicity will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0. Observed toxicities/adverse events will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune Biomarker Expression | Up to 6 months | Changes (%) in PD1 expression compared to baseline by immunohistochemistry Changes (%) in PD-L1 expression compared to baseline by immunohistochemistry Changes (%) CTLA-4 expression compared to baseline by immunohistochemistry Changes (%) CD8 cell quantification compared to baseline by Immunohistochemistry |
| Optimal biologic dose | Up to 3 months | Defined as 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%). |
| Response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Up to 6 months | Will estimate the response rate by the percent of evaluable patients and its 95% confidence interval (C.I.) by the exact method. |
| Response rate based on immune related iRECIST | Up to 6 months | Will estimate the response rate by the percent of evaluable patients and its 95% C.I. by the exact method. |
| Progression free survival | Up to 1 year | Will be estimated using the Kaplan-Meier product-limit method. |
| Clinical benefit rate | Up to 6 months | Percentage of patients who achieved Partial Response/ Complete Response/ Stable disease at 6 months |
| Event-free survival | Up to 3 years | Event-free survival (EFS): defined as the duration of time from start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier. |
| Duration of response | Up to 3 years | Duration of response (DOR): defined as the time from the first achievement of PR and CR to time of PD. |
| Overall survival | Up to 3 years | Will be estimated using the Kaplan-Meier product-limit method. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJamie Rand
City of Hope Medical Center
Outcome results
None listed