CF33-hNIS-antiPDL1 for the Treatment of Metastatic Triple Negative Breast Cancer
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|ClinicalTrials.gov Identifier: NCT05081492|
Recruitment Status : Recruiting
First Posted : October 18, 2021
Last Update Posted : March 18, 2022
|Condition or disease||Intervention/treatment||Phase|
|Anatomic Stage IV Breast Cancer AJCC v8 Metastatic Triple-Negative Breast Carcinoma Prognostic Stage IV Breast Cancer AJCC v8||Biological: Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody||Phase 1|
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.
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||78 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||October 18, 2021|
|Estimated Primary Completion Date :||October 1, 2023|
|Estimated Study Completion Date :||October 1, 2023|
Experimental: Treatment (CF33-hNIS-antiPDL1)
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.
Biological: Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody
- 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.
- Immune Biomarker Expression [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 1 year ]Will be estimated using the Kaplan-Meier product-limit method.
- Clinical benefit rate [ Time Frame: Up to 6 months ]Percentage of patients who achieved Partial Response/ Complete Response/ Stable disease at 6 months
- Event-free survival [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 3 years ]Will be estimated using the Kaplan-Meier product-limit method.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05081492
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Yuan Yuan 626-256-4673 Yuyuan@coh.org|
|Principal Investigator: Yuan Yuan|
|Principal Investigator:||Yuan Yuan||City of Hope Medical Center|