This phase Ib/II trial studies how well dendritic cell therapy after cryosurgery in combination with pembrolizumab works in treating patients with stage III-IV melanoma that cannot be removed by surgery. Vaccines made from a person's white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells. Cryosurgery, also known as cryoablation or cryotherapy, kills tumor cells by freezing them. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Giving dendritic cell therapy after cryosurgery in combination with pembrolizumab may work better in treating patients with melanoma.
PRIMARY OBJECTIVES OF PHASE I portion of the trial: To establish the safety and tolerability of the proposed treatment schedule in order to move it forward into the Phase II portion of the trial. PRIMARY OBJECTIVES OF PHASE II portion of the trial: I. To determine the objective response rate (ORR) of pembrolizumab combined with cryoablation and intratumoral mature dendritic cells (mDCs) in patients with metastatic melanoma that has failed to respond or has stopped responding to initial therapy with a PD-1 axis-blocking monoclonal antibody. SECONDARY OBJECTIVES: I. To assess the safety profile of pembrolizumab combined with cryoablation and intratumoral mDCs in patients with metastatic melanoma that have failed to respond or have stopped responding to initial therapy with a PD-1 axis-blocking monoclonal antibody. II. To determine median progression-free survival (PFS) obtained with this approach in this patient population. III. To determine median overall survival (OS) obtained with this approach in this patient population. TERTIARY OBJECTIVES: I. To quantitate tumor infiltrating lymphocytes (TILs) in tumor biopsies prior to and following cryoablation and intratumoral mDCs. II. To measure PD-L1 levels in tumor biopsies and blood biopsies prior to and following cryoablation and to assess whether a change in PD-L1 levels differ among those patients who met the criteria for clinical benefit (progression-free and on study for at least 6 months) and those who do not. III. To measure peripheral blood mononuclear cells (PBMC) proliferation and function after coculture with frozen tumor before and after intratumoral mDC injection.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Undergo cryosurgery
IV
apheresis
Intra-tumoral injection
Mayo Clinic
Rochester, Minnesota, United States
Number of Participants Who Developed a DLT During the First 3 Cycles of Treatment.
The primary outcome of the Phase I portion of this trial was to establish the tolerability of the proposed treatment schedule in order to move it forward into the Phase II portion of the trial. A maximum of 6 patients was to be enrolled onto the Schedule 1. If at most one of these 6 patients developed a DLT during the first 3 treatment cycles, then Schedule #1 would be carried forward to the Phase II portion of the trial. If not, then an additional 6 patients would be treated with a modified Schedule 1 where Pembrolizumab was eliminated from cycles 2 \& 3. Dose-limiting toxicity (DLT) were defined as the following possibly, probably, or definitely related AEs to protocol therapy during first 3 treatment cycles: Grade 3+ infusion reactions, acute kidney injury, chronic kidney disease, pneumonitis; or Grade 2 infusion reactions, acute kidney injury, chronic kidney disease or pneumonitis that does not resolve to Grade 0-1 within 21 days.
Time frame: Up to 3 months (3 cycles of 21 days and an additional 7 days for Cycle 1)
Incidence of Adverse Events
Assessed using Common Terminology Criteria for Adverse Events (CTCAE).
Time frame: 30 months (through study completion)
Overall Survival
Time from registration to death due to any cause
Time frame: 30 months (through study completion)
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