search
Back to results

CF33-hNIS-antiPDL1 for the Treatment of Metastatic Triple Negative Breast Cancer

Primary Purpose

Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anatomic Stage IV Breast Cancer AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • City of Hope Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (CF33-hNIS-antiPDL1)

Arm Description

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.

Outcomes

Primary Outcome Measures

Incidence of adverse events
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 Outcome Measures

Immune Biomarker Expression
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
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
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
Will estimate the response rate by the percent of evaluable patients and its 95% C.I. by the exact method.
Progression free survival
Will be estimated using the Kaplan-Meier product-limit method.
Clinical benefit rate
Percentage of patients who achieved Partial Response/ Complete Response/ Stable disease at 6 months
Event-free survival
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
Duration of response (DOR): defined as the time from the first achievement of PR and CR to time of PD.
Overall survival
Will be estimated using the Kaplan-Meier product-limit method.

Full Information

First Posted
October 4, 2021
Last Updated
May 3, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI), Imugene Limited
search

1. Study Identification

Unique Protocol Identification Number
NCT05081492
Brief Title
CF33-hNIS-antiPDL1 for the Treatment of Metastatic Triple Negative Breast Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 18, 2021 (Actual)
Primary Completion Date
December 1, 2023 (Anticipated)
Study Completion Date
December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI), Imugene Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
78 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (CF33-hNIS-antiPDL1)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody
Other Intervention Name(s)
CF33 Expressing hNIS-Anti-PD-L1 Antibody, CF33-hNIS-antiPDL1
Intervention Description
Given IT
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
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.
Time Frame
Up to 30 days
Secondary Outcome Measure Information:
Title
Immune Biomarker Expression
Description
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
Time Frame
Up to 6 months
Title
Optimal biologic dose
Description
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%).
Time Frame
Up to 3 months
Title
Response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Description
Will estimate the response rate by the percent of evaluable patients and its 95% confidence interval (C.I.) by the exact method.
Time Frame
Up to 6 months
Title
Response rate based on immune related iRECIST
Description
Will estimate the response rate by the percent of evaluable patients and its 95% C.I. by the exact method.
Time Frame
Up to 6 months
Title
Progression free survival
Description
Will be estimated using the Kaplan-Meier product-limit method.
Time Frame
Up to 1 year
Title
Clinical benefit rate
Description
Percentage of patients who achieved Partial Response/ Complete Response/ Stable disease at 6 months
Time Frame
Up to 6 months
Title
Event-free survival
Description
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.
Time Frame
Up to 3 years
Title
Duration of response
Description
Duration of response (DOR): defined as the time from the first achievement of PR and CR to time of PD.
Time Frame
Up to 3 years
Title
Overall survival
Description
Will be estimated using the Kaplan-Meier product-limit method.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 =< 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jamie Rand
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jamie Rand
Phone
626-256-4673
Email
jrand@coh.org
First Name & Middle Initial & Last Name & Degree
Jamie Rand

12. IPD Sharing Statement

Learn more about this trial

CF33-hNIS-antiPDL1 for the Treatment of Metastatic Triple Negative Breast Cancer

We'll reach out to this number within 24 hrs