A Phase II Study of Intratumorally Injected Autologous Dendritic Cells (DCs) in PD-L1-Negative Treatment Naïve and in Refractory Metastatic Triple Negative Breast Cancer Patients
Overview
- Phase
- Phase 2
- Intervention
- Alpha-type-1 Polarized Dendritic Cells
- Conditions
- Anatomic Stage III Breast Cancer AJCC v8
- Sponsor
- Roswell Park Cancer Institute
- Enrollment
- 19
- Locations
- 1
- Primary Endpoint
- Incidence of adverse events
- Status
- Withdrawn
- Last Updated
- last year
Overview
Brief Summary
This phase II trial tests the safety, side effects, and whether dendritic cell-based treatment and pembrolizumab work in treating patients with triple negative breast cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). The term triple-negative breast cancer refers to the fact that the cancer cells don't have estrogen or progesterone receptors (ER or PR) and also don't make any or too much of the protein called HER2 (the cells test "negative" on all 3 tests). Dendritic cell-based treatment works by boosting the immune system (a system in our bodies that protects us against infection) to recognize and destroy the cancer cells. Pembrolizumab, is an immune checkpoint inhibitor drug, that works by targeting molecules that act as a check and balance system for immune responses. Immune checkpoint inhibitor drugs are 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-based therapy and pembrolizumab may decrease symptoms and improve quality of life in patients with triple negative breast cancer.
Detailed Description
PRIMARY OBJECTIVE: I. To determine the clinical efficacy and safety and tolerability of a combination of intratumorally injected autologous dendritic cells (DCs) and pembrolizumab in PD-L1 negative treatment-naive and refractory metastatic triple negative breast cancer patients. SECONDARY OBJECTIVES: I. To assess progression-free survival and overall survival in metastatic triple negative breast cancer patients that received the combination of intratumorally injected autologous DCs and pembrolizumab. II. To assess the clinical efficacy in the non-injected target lesion (optional biopsies for this lesion). OUTLINE: Patients undergo leukapheresis over 90 minutes. Patients then receive ST-alpha-DC1 intratumorally (IT) on days 1, 8, and 50 in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab intravenously (IV) on days 8, 29, 50, and 71 in the absence of disease progression or unacceptable toxicity. Patients who are receiving clinical benefit from treatment at the end of day 85, may continue to receive pembrolizumab IV every 3 weeks beyond the 4 study doses. Patients also undergo tumor biopsies on days 1, 8, and 50 and computed tomography (CT) scans at baseline and days 50 and 85. After completion of study treatment, patients are followed up at 30 and 90 days after the last dose of study drug, and then every 3 months for up to 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age \>= 18 years of age
- •Pathologically confirmed diagnosis of unresectable or metastatic triple negative breast cancer (TNBC) with no curative treatment options
- •At least 2 target lesions present per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at least one of which is amenable to biopsy and injection
- •PD-L1 negative metastatic TNBC patients who are treatment naive in the first linen metastatic setting are eligible
- •Both PD-L1 positive and PD-L1 negative metastatic TNBC patients in the second line setting and beyond are eligible
- •Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =\< 2
- •Platelets \>= 75,000/uL
- •Hemoglobin \>= 8 g/dL
- •Absolute Neutrophil Count (ANC) \>= 1500/uL
- •Creatinine =\< 1.5 x upper limit of normal (ULN) OR creatinine clearance \>= 30 mL/min for participant with creatinine levels \>1.5 x institutional ULN
Exclusion Criteria
- •Participants currently treated with systemic immunosuppressive agents, including steroids (\> than equivalent of 10 mg daily of prednisone) are ineligible until 3 weeks after removal from immunosuppressive treatment
- •Patients with active autoimmune disease or history of transplantation
- •Cardiac risk factors including:
- •Patients experiencing cardiac event(s) (acute coronary syndrome, myocardial infarction, or ischemia) within 3 months of signing consent
- •Patients with a New York Heart Association classification of III or IV
- •Pregnant or nursing female participants
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
- •Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\<2 weeks of radiotherapy) to non-CNS disease
- •Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
Arms & Interventions
Treatment (ST-alpha-DC1, pembrolizumab)
Patients undergo leukapheresis over 90 minutes. Patients then receive ST-alpha-DC1 IT on days 1, 8, and 50 in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV on days 8, 29, 50, and 71 in the absence of disease progression or unacceptable toxicity. Patients who are receiving clinical benefit from treatment at the end of day 85, may continue to receive pembrolizumab IV every 3 weeks beyond the 4 study doses. Patients also undergo tumor biopsies on days 1, 8, and 50 and CT scans at baseline and days 50 and 85.
Intervention: Alpha-type-1 Polarized Dendritic Cells
Treatment (ST-alpha-DC1, pembrolizumab)
Patients undergo leukapheresis over 90 minutes. Patients then receive ST-alpha-DC1 IT on days 1, 8, and 50 in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV on days 8, 29, 50, and 71 in the absence of disease progression or unacceptable toxicity. Patients who are receiving clinical benefit from treatment at the end of day 85, may continue to receive pembrolizumab IV every 3 weeks beyond the 4 study doses. Patients also undergo tumor biopsies on days 1, 8, and 50 and CT scans at baseline and days 50 and 85.
Intervention: Biopsy
Treatment (ST-alpha-DC1, pembrolizumab)
Patients undergo leukapheresis over 90 minutes. Patients then receive ST-alpha-DC1 IT on days 1, 8, and 50 in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV on days 8, 29, 50, and 71 in the absence of disease progression or unacceptable toxicity. Patients who are receiving clinical benefit from treatment at the end of day 85, may continue to receive pembrolizumab IV every 3 weeks beyond the 4 study doses. Patients also undergo tumor biopsies on days 1, 8, and 50 and CT scans at baseline and days 50 and 85.
Intervention: Computed Tomography
Treatment (ST-alpha-DC1, pembrolizumab)
Patients undergo leukapheresis over 90 minutes. Patients then receive ST-alpha-DC1 IT on days 1, 8, and 50 in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV on days 8, 29, 50, and 71 in the absence of disease progression or unacceptable toxicity. Patients who are receiving clinical benefit from treatment at the end of day 85, may continue to receive pembrolizumab IV every 3 weeks beyond the 4 study doses. Patients also undergo tumor biopsies on days 1, 8, and 50 and CT scans at baseline and days 50 and 85.
Intervention: Leukapheresis
Treatment (ST-alpha-DC1, pembrolizumab)
Patients undergo leukapheresis over 90 minutes. Patients then receive ST-alpha-DC1 IT on days 1, 8, and 50 in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV on days 8, 29, 50, and 71 in the absence of disease progression or unacceptable toxicity. Patients who are receiving clinical benefit from treatment at the end of day 85, may continue to receive pembrolizumab IV every 3 weeks beyond the 4 study doses. Patients also undergo tumor biopsies on days 1, 8, and 50 and CT scans at baseline and days 50 and 85.
Intervention: Pembrolizumab
Treatment (ST-alpha-DC1, pembrolizumab)
Patients undergo leukapheresis over 90 minutes. Patients then receive ST-alpha-DC1 IT on days 1, 8, and 50 in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV on days 8, 29, 50, and 71 in the absence of disease progression or unacceptable toxicity. Patients who are receiving clinical benefit from treatment at the end of day 85, may continue to receive pembrolizumab IV every 3 weeks beyond the 4 study doses. Patients also undergo tumor biopsies on days 1, 8, and 50 and CT scans at baseline and days 50 and 85.
Intervention: Quality-of-Life Assessment
Outcomes
Primary Outcomes
Incidence of adverse events
Time Frame: Up to 30 days after last dose
Will be assessed using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and will be summarized by attribution and grade using frequencies and relative frequencies.
Objective responses rate (ORR)
Time Frame: Up to 2 years
Will be assessed by immune related response criteria (iRECIST).
Secondary Outcomes
- Overall survival (OS)(Up to 2 years)
- Progression-free survival (PFS)(Up to 2 years)
- Objective response rate(Up to 2 years)