A Phase 1 Study of MK-3475 (pembrolizumab) in Combination with Recombinant Interleukin-12 in Patients with Solid Tumors (NCI#10061)
Johns Hopkins Kimmel Cancer Center in Baltimore
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.
INCLUSION CRITERIA:-Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard FDA-approved systemic curative or palliative antitumor therapies do not exist or are no longer effective or for which MK-3475 (pembrolizumab) is FDA-approved as standard of care therapy-ECOG performance status equal to less than 1-Life expectancy of greater than 12 weeks-Normal organ and marrow function-Patients must have measurable disease based on RECIST 1.1-Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation-Female patients of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication-Patients who are HIV positive may participate IF they are stable on their anti-retroviral regimen, are healthy from an HIV perspective, have an undetectable viral load, have a CD4 count of greater than 250 cells/mcL, and must not be receiving prophylactic therapy for an opportunistic infectionEXCLUSION CRITERIA:-Patients who have had chemotherapy, targeted small molecule therapy, or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier-Patients who are currently participating in or have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment-Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment-Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier-Has a known additional malignancy that is progressing or requires active treatment-Patients with known brain active and untreated metastases-Patients with carcinomatous meningitis should also be excluded-History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 (pembrolizumab) and/or rhIL-12 or other agents used in study-Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents-Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator-Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial-Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)-Patients on any systemic corticosteroid therapy within one week before the planned date for first dose on study would not be eligible-Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements-Is pregnant or breastfeeding-Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)-Has received a live vaccine within 30 days prior to the first dose of trial treatment
Patients receive recombinant interleukin-12 SC on days 2, 5, 9, and 12 and pembrolizumab 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.
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