This phase IIa trial studies how well dendritic cell vaccines against Her2/Her3 and pembrolizumab work for the treatment of triple negative breast cancer or HER2+ breast cancer or HER+ Breast cancer that has spread to the brain (brain metastasis). Dendritic cell vaccines work by boosting the immune system (a system in the body that protect against infection) to recognize and destroy the cancer cells. . Pembrolizumab is an "immune checkpoint inhibitor" which is designed to either "unleash" or "enhance" the cancer immune responses that already exist by either blocking inhibitory molecules" or by activating stimulatory molecules. Giving dendritic cell vaccines and pembrolizumab may shrink the cancer.
Not a woman of childbearing potential (WOCBP)
A WOCBP who agrees to follow contraceptive guidance
WOCBP must agree to use acceptable birth control methods for the duration of the study and until persistence of the study drug is no longer detected in the peripheral blood:this may be a period of several years. Methods for acceptable birth control include: condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception; it is recommended that a combination of two methods be used. NOTE: If the risk of conception exists, patients must agree to use highly effective contraception throughout the study and for at least two years following the last study treatment administration
At initial screening prior to eligibility confirmation
Any condition which might confound the results of the study, interfere with the subject's participation for full participation (for the full duration of the study) or in the Investigator's opinion deems the participant an unsuitable candidate for the study
Symptomatic brain metastases. Any neurologic symptoms present must have resolved with local therapy by the time of administration of study drugs
May not be receiving any other investigational agents and may not have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of DC vaccine treatment
Has had prior chemotherapy or targeted small molecule therapy (except treatment mentioned in inclusion criteria 17) within 4 weeks or 5 half-lives (whichever is sooner) prior to start of treatment (first DC vaccine) or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent. Previous radiation to extracranial sites may be completed at any time prior to initiation of study drugs (first DC vaccine) with a 2-week washout is required.
Single group
Anti-HER2/HER3 Dendritic Cell Vaccine
Biological/VaccineGiven ID
Pembrolizumab
Biological/VaccineGiven IV
Central nervous system (CNS) objective response rate (ORR)
Assessed per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group. Will be summarized using frequencies and relative frequencies. A 90% confidence interval about the true ORR will be obtained using Jeffrey's prior method.
Volumetric quantification of brain metastases
Non-CNS (i.e. of systemic disease) response rate
Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Median CNS progression free survival (PFS)
Will be summarized using frequencies and relative frequencies. A 90% confidence interval about the true response rate will be obtained using Jeffrey's prior method.
Non-CNS PFS
Will be summarized using frequencies and relative frequencies. A 90% confidence interval about the true response rate will be obtained using Jeffrey's prior method.
Changes in tumor circulating tumor lymphocyte (CTL)s
Will be summarized by timepoint using the mean and standard deviation; and graphically using box- or dot-plots. The mean change (pre- to post-treatment) in biomarker values will be evaluated using a two-sided, permutation paired t-tests. The correlation between different biomarkers or changes in biomarkers will be evaluated using the Spearman correlation coefficient. The association between biomarker values (baseline or change) and response will be evaluated using logistic regression models.
Changes in tumor PDL-1 expression
Will be summarized by timepoint using the mean and standard deviation; and graphically using box- or dot-plots. The mean change (pre- to post-treatment) in biomarker values will be evaluated using a two-sided, permutation paired t-tests. The correlation between different biomarkers or changes in biomarkers will be evaluated using the Spearman correlation coefficient. The association between biomarker values (baseline or change) and response will be evaluated using logistic regression models.
Changes in cytokine expression
Will be summarized by timepoint using the mean and standard deviation; and graphically using box- or dot-plots. The mean change (pre- to post-treatment) in biomarker values will be evaluated using a two-sided, permutation paired t-tests. The correlation between different biomarkers or changes in biomarkers will be evaluated using the Spearman correlation coefficient. The association between biomarker values (baseline or change) and response will be evaluated using logistic regression models.
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Roswell Park Cancer Institute
Lead sponsor
United States Department of Defense
Collaborator
