Anatomic Stage IV Breast Cancer AJCC v8Phase 1NCT05081492
CF33-hNIS-antiPDL1 for the Treatment of Metastatic Triple Negative Breast Cancer
A Phase 1 study testing Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Triple-Negative Breast Carcinoma, run by City of Hope Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8
- What is being tested?
- Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Oct 2021to 1 Mar 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
- Conditions
- Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8
- Being tested
- Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 AntibodyBiological
Also called CF33 Expressing hNIS-Anti-PD-L1 Antibody, CF33-hNIS-antiPDL1
Given IT
| Study group | Role | What they receive |
|---|---|---|
| Treatment (CF33-hNIS-antiPDL1) | Experimental | 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. Receives: Biological: Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 30 days
Secondary outcomes (9)
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
Measured: Up to 6 months
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%).
Measured: Up to 3 months
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.
Measured: Up to 6 months
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.
Measured: Up to 6 months
Progression free survival
Will be estimated using the Kaplan-Meier product-limit method.
Measured: Up to 1 year
Clinical benefit rate
Percentage of patients who achieved Partial Response/ Complete Response/ Stable disease at 6 months
Measured: Up to 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.
Measured: Up to 3 years
Duration of response
Duration of response (DOR): defined as the time from the first achievement of PR and CR to time of PD.
Measured: Up to 3 years
Overall survival
Will be estimated using the Kaplan-Meier product-limit method.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2021
- Study start18 Oct 2021
- Primary completion1 Mar 2027 (estimated)
- Study completion1 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Anatomic Stage IV Breast Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Imugene Limited
- Responsible party
- Sponsor
- Investigators
- Jamie Rand, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05081492
- Sponsor's protocol ID
- 21094
- Other IDs
- NCI-2021-08983, 21094, P30CA033572
- Status last verified
- Apr 2026
- First submitted
- 4 Oct 2021
- Last updated
- 17 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Rand J, Yamauchi D, Chaurasiya S, Zhang J, Deshpande S, Chong L, Seiz A, Meisen H, Fong Y, Yuan Y. hNIS-based imaging to monitor treatment with the novel oncolytic virus CF33-hNIS-antiPDL1 in humans with advanced triple negative breast cancer. Front Oncol. 2025 Aug 25;15:1565244. doi: 10.3389/fonc.2025.1565244. eCollection 2025.
PubMed 40933893Yuan Y, Egelston C, Colunga Flores O, Chaurasiya S, Lin D, Chang H, Chong LMO, Seiz A, Shah M, Meisen WH, Tang A, Martinez N, Pickett W, Murga M, Yost SE, Stewart D, Zhang J, Ede N, Modi B, Kessler J, Rand J, Fong Y. CF33-hNIS-anti-PD-L1 oncolytic virus followed by trastuzumab-deruxtecan in a patient with metastatic triple negative breast cancer: a case study. Ther Adv Med Oncol. 2023 Nov 10;15:17588359231210675. doi: 10.1177/17588359231210675. eCollection 2023.
PubMed 38028143
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05081492
- Acronym / sponsor ID
- 21094
- Conditions
- Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 9 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Imugene Limited
- Study start
- 18 Oct 2021 (actual)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 1 Mar 2027 (estimated)
- First posted
- 18 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (CF33-hNIS-antiPDL1) | Experimental | Biological: Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 AntibodyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Documented informed consent of the participant and/or legally authorized representative
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 AntibodyAlso: CF33 Expressing hNIS-Anti-PD-L1 Antibody, CF33-hNIS-antiPDL1Given IT | Biological | Treatment (CF33-hNIS-antiPDL1) |
Primary outcome
Incidence of adverse events
Time frame: 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.
9 secondary outcomes
Immune Biomarker Expression
Time frame: Up to 6 months
Optimal biologic dose
Time frame: Up to 3 months
Response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time frame: Up to 6 months
Response rate based on immune related iRECIST
Time frame: Up to 6 months
Progression free survival
Time frame: Up to 1 year
Clinical benefit rate
Time frame: Up to 6 months
Event-free survival
Time frame: Up to 3 years
Duration of response
Time frame: Up to 3 years
Overall survival
Time frame: Up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Derived from this study: PubMed 40933893Rand J, Yamauchi D, Chaurasiya S, Zhang J, Deshpande S, Chong L, Seiz A, Meisen H, Fong Y, Yuan Y. hNIS-based imaging to monitor treatment with the novel oncolytic virus CF33-hNIS-antiPDL1 in humans with advanced triple negative breast cancer. Front Oncol. 2025 Aug 25;15:1565244. doi: 10.3389/fonc.2025.1565244. eCollection 2025.
- Derived from this study: PubMed 38028143Yuan Y, Egelston C, Colunga Flores O, Chaurasiya S, Lin D, Chang H, Chong LMO, Seiz A, Shah M, Meisen WH, Tang A, Martinez N, Pickett W, Murga M, Yost SE, Stewart D, Zhang J, Ede N, Modi B, Kessler J, Rand J, Fong Y. CF33-hNIS-anti-PD-L1 oncolytic virus followed by trastuzumab-deruxtecan in a patient with metastatic triple negative breast cancer: a case study. Ther Adv Med Oncol. 2023 Nov 10;15:17588359231210675. doi: 10.1177/17588359231210675. eCollection 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jamie Rand principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Triple-Negative Breast Carcinoma, run by City of Hope Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Up to 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05081492, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.