Pembrolizumab and Recombinant Interleukin-12 in Treating Patients With Solid Tumors
A Phase 1 Study of Pembrolizumab (MK-3475) in Combination With Recombinant Interleukin-12 in Patients With Solid Tumors
4 other identifiers
interventional
36
1 country
27
Brief Summary
This phase I trial studies the side effects and best dose of pembrolizumab and recombinant interleukin-12 in treating patients with solid tumors. 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. 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 than giving pembrolizumab alone in treating patients with solid tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started May 2018
Longer than P75 for phase_1
27 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 24, 2017
CompletedFirst Posted
Study publicly available on registry
January 25, 2017
CompletedStudy Start
First participant enrolled
May 30, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2026
May 19, 2026
May 1, 2026
8.5 years
January 24, 2017
May 16, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose (MTD)
Up to 5 years
Recommended phase 2 dose
Up to 5 years
Secondary Outcomes (4)
Incidence of adverse events
Up to 30 days after last dose
Progression free survival
From start of treatment to time of progression or death, whichever comes, first assessed up to 5 years
Overall response rate
From start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started), assessed up to 5 years
CD8+ T cell infiltration
Up to 2 cycles of treatment
Other Outcomes (1)
Biomarker analysis
Up to 5 years
Study Arms (1)
Treatment (recombinant interleukin-12, pembrolizumab)
EXPERIMENTALPatients receive recombinant interleukin-12 SC on days 2, 5, 9, and 12 and pembrolizumab IV over 30 minutes on day 8 of cycle 1 and day 1 of subsequent cycles. Treatment continues for 28 days for cycle 1 and repeats every 21 days for subsequent cycles for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patient then receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 8 additional cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, PET, and MRI, as well as collection of blood during screening, on study, and during follow-up. Patients also undergo a tumor biopsy during screening and on study.
Interventions
Undergo collection of blood
Undergo a PET scan
Undergo a tumor biopsy
Undergo a CT scan
Given SC
Undergo a MRI
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed malignancy that is metastatic or unresectable
- Eligibility is restricted to patients who have tumors for which there is a Food and Drug Administration (FDA)-approved indication for anti-PD-(L)1 therapy. Patients must have received and have progressed past anti-PD(L)1 singly or in combination. There is no restriction on the number of prior lines of therapy. Anti-PD-(L)1 therapy need not be the most recent therapy received
- NOTE: Prior to slot reservation, sites must provide the following information to ETCTN10061@upmc.edu for study chair review: histology, nature of prior therapy (therapies) and indication for prior PD-(L)1 therapy
- Age \>= 18 years
- Because no dosing or adverse event data are currently available on the use of pembrolizumab (MK-3475) in combination with rhIL-12 in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
- Life expectancy of greater than 12 weeks
- Leukocytes \>= 2,000/mcL (within 28 days of treatment initiation)
- Absolute neutrophil count \>= 1,500/mcL (within 28 days of treatment initiation)
- Platelets \>= 100,000/mcL (within 28 days of treatment initiation)
- Hemoglobin \>= 9 g/dL OR \>= 5.6 mmol/L (within 28 days of treatment initiation)
- Serum total bilirubin =\< upper limit of normal (ULN) OR direct bilirubin =\< ULN for patients with total bilirubin levels \> ULN; (except patients with Gilbert's syndrome, who must have a total bilirubin less than 3.0 mg/dL) (within 28 days of treatment initiation)
- Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =\< 2.5 x institutional ULN (within 28 days of treatment initiation)
- Serum creatinine =\< 1.5 x ULN OR measured or calculated creatinine clearance (CrCl) (glomerular filtration rate \[GFR\] can also be used in place of creatinine or CrCl) \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN (within 28 days of treatment initiation)
- Creatinine clearance should be calculated per institutional standard
- +22 more criteria
You may not qualify if:
- Patients with a secondary active hematological malignancy including but not limited to chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Hodgkins lymphoma, non-Hodgkins lymphoma (NHL)
- Patients with a prior history of autoimmune cytopenias of any etiology including hemolytic anemia, (AIHA), idiopathic thrombocytopenia purpura (ITP), and/or other cytopenia are excluded
- Patients who have had chemotherapy, targeted small molecule therapy, or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of trial treatment, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Note: Patients with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
- Note: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- 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 trial 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 (i.e., =\< grade 1 or at baseline) from adverse events (AEs) due to agents administered more than 4 weeks earlier; non-clinically significant adverse events may be considered as an exception after discussion with and approval by the principal investigator
- Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
- Patients with known active and untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Patients with primary brain tumors or carcinomatous meningitis should also be excluded
- Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not requiring steroids for at least 7 days prior to trial treatment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab (MK-3475) 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; patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; patients with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
- 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
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (27)
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UCSF Medical Center-Mount Zion
San Francisco, California, 94115, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510, United States
Yale University
New Haven, Connecticut, 06520, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Diwakar Davar
University of Pittsburgh Cancer Institute LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 24, 2017
First Posted
January 25, 2017
Study Start
May 30, 2018
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
December 1, 2026
Last Updated
May 19, 2026
Record last verified: 2026-05