A Phase 1 Study of MK-3475 (Pembrolizumab) in Combination with Recombinant Interleukin-12 in Patients with Solid Tumors
18 Years and older, Male and Female
This phase I trial studies the side effects and best dose of pembrolizumab and recombinant interleukin-12 in treating patients with solid tumors. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Recombinant interleukin-12 may kill tumor cells by blocking blood flow to the tumor and by stimulating white blood cells to kill tumor cells. Giving pembrolizumab and recombinant interleukin-12 may work better in treating patients with solid tumors.
I. Establish the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of recombinant human interleukin (rhIL)-12 in combination with MK-3475 (pembrolizumab).
I. Evaluate the safety of the regimen by continuously monitoring adverse events that will be documented utilizing Common Terminology Criteria for Adverse Events (CTCAE) version (v).5.0.
II. Evaluate the overall response rate (Response Evaluation Criteria in Solid Tumors [RECIST] v.1.1) and the progression free survival of patients enrolled on the study.
II. Measure CD8+ T cell infiltration by immunohistochemistry in tumor biopsies obtained at baseline, after one week of rhIL-12 and after 2 cycles of MK-3475 (pembrolizumab) in combination with rhIL-12.
IV. Conduct exploratory translational laboratory correlative studies utilizing banked biospecimens (tumor and blood) obtained at baseline and during therapy.
OUTLINE: This is a dose-escalation study of recombinant interleukin-12.
Patients receive recombinant interleukin-12 subcutaneously (SC) on days 2, 5, 9, and 12 and pembrolizumab intravenously (IV) over 30 minutes on day 8 of course 1 and day 1 of subsequent courses. Treatment continues for 28 days for course 1 and repeats every 21 days for subsequent courses for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients then receive recombinant interleukin-12 SC on days 2, 5, 9, and 12. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 3 years.