Vaccine Therapy Plus Pembrolizumab in Treating Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer
brief summary
This phase I/II trial tests the safety, side effects, best dose, and effectiveness of multi-epitope folate receptor alpha-loaded dendritic cell vaccine (FRalphaDC) with pembrolizumab in treating patients with ovarian, fallopian tube, or primary peritoneal cancer (collectively known as ovarian cancer) that that has come back (after a period of improvement) (recurrent). Ovarian cancer is the most lethal gynecologic malignancy in the United States. While the majority of patients achieve a remission from ovarian cancer with the combination of aggressive cytoreductive surgery and cytotoxic chemotherapy, over 80% of patients develop recurrence within 3 years of completion of treatment. Additional treatments are needed for recurrence, but the standard treatment modalities are non-curative in nature due to the development of drug resistance. As such, there is a great unmet need for treatment strategies that utilize new mechanisms to which drug resistance does not develop. FRalphaDC is a dendritic cell vaccine that is made from the white blood cells collected from a procedure call apheresis. The white blood cells are treated to make dendritic cells, which will then be incubated with peptides, which are pieces of a protein known as "folate receptor alpha" (FRalpha), a protein that is found in high levels on ovarian cancer cells. Dendritic cell vaccines work by boosting the immune system (a system in the body that protect against infection) to recognize and destroy the tumor cells by targeting the FRalpha protein. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving FRalphaDC vaccine with pembrolizumab may be a safe and effective treatment for recurrent ovarian cancer.
detailed description
PRIMARY OBJECTIVES:
I. To determine whether the combination of FRalphaDCs and pembrolizumab has an acceptable toxicity profile in patients with recurrent ovarian cancer (OC). (Phase I) II. To measure the confirmed objective response rate (ORR) to the combination of FRalphaDCs and pembrolizumab in patients with recurrent OC. (Phase II)
SECONDARY OBJECTIVES:
I. To estimate the disease control rate (DCR-percentage of patients achieving a complete response, partial response, or stable disease) of the combination of FRalphaDCs and pembrolizumab in patients with recurrent OC.
II. To estimate the duration of response (DoR) in patients with recurrent OC treated with the combination of FRalphaDCs and pembrolizumab.
III. To estimate the progression-free survival (PFS) of patients with recurrent OC treated with the combination of FRalphaDCs and pembrolizumab.
IV. To estimate the overall survival (OS) of patients with recurrent OC treated with the combination of FRalphaDCs and pembrolizumab.
2.25 To characterize the adverse event (AE) profile in patients with recurrent OC treated with the combination of FRalphaDCs and pembrolizumab.
CORRELATIVE OBJECTIVES:
I. To determine whether the combination of FRalphaDCs and pembrolizumab induces an increase in the frequency of FRalpha-specific IL-17-secreting T cells (Th17s) in patients with recurrent OC.
II. Characterize the T cell and antibody responses to FRalpha and assess the association between the emergence of immunity and recurrence-free (RFS).
III. To determine whether the combination of FRalphaDCs and pembrolizumab induces an increase in the frequency of FRalpha-specific IFNgamma-secreting T cells (Th1s) in patients with recurrent OC.
IV. To determine whether the combination of FRalphaDCs and pembrolizumab induces an increase in the frequency of FRalpha-specific IgG antibodies in patients with recurrent OC.
V. To determine whether the combination of FRalphaDCs and pembrolizumab induces changes in the immune microenvironment of ovarian tumors.
official title
MC220601, Folate Receptor Alpha Dendritic Cells (FRαDCs) Plus Pembrolizumab for Patients With Advanced Stage Ovarian Cancer (FRAPPE)