A Phase I, First-in-Human Study of Intratumoral Administration of CF33-hNIS-antiPDL1, A Novel Chimeric Oncolytic Poxvirus Encoding Human Sodium Iodide Symporter (HNIS) in Patients With Metastatic Triple Negative Breast Cancer
| Registry | NCT05081492 |
|---|---|
| Status | Active not recruiting |
| Phase | Phase 1 |
| Study type | Interventional; na, single group, masking: none, treatment |
| Enrollment | 9 (Actual) |
| Sponsor | City of Hope Medical Center (Other); collaborators: National Cancer Institute (NCI), Imugene Limited |
| Conditions | Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8 |
| Interventions | Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody (Biological) |
| Dates | start 2021-10-18, primary completion 2027-03-01 (estimated), completion 2027-03-01 (estimated), first posted 2021-10-18, last updated 2026-04-17 |
| Locations | 1 site in United States |
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All trials for Anatomic Stage IV Breast Cancer AJCC v8 All trials for Metastatic Triple-Negative Breast Carcinoma All trials of Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Treatment (CF33-hNIS-antiPDL1) | Experimental | Biological: Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody | Patients receive CF33-hNIS-antiPDL1 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. |
Sex: All, ages: 18 Years to any
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)
| Facility | City | Country | Status |
|---|---|---|---|
| City of Hope Medical Center | Duarte, California | United States |
NIH grants: P30CA033572