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Pembrolizumab and Recombinant Interleukin-12 in Treating Patients with Solid Tumors

Cancer Type
Solid Tumor
Unknown Primary
Trial Phase
Phase I
18 Years and older, Male and Female
Study Type
Protocol IDs
10061 (primary)
HCC 17-003
Study Sponsor
University of Pittsburgh Cancer Institute LAO


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.


I. Establish the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of edodekin alfa (recombinant human interleukin [rhIL]-12) in combination with pembrolizumab (MK-3475).

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.
III. Measure CD8+ T cell infiltration by immunohistochemistry in tumor biopsies obtained pre-treatment, after one week of rhIL-12 and after 2 cycles of pembrolizumab (MK-3475) in combination with rhIL-12.

I. Conduct exploratory translational laboratory correlative studies utilizing banked biospecimens (tumor, blood, and stool) obtained pre-treatment 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 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 computed tomography (CT), positron emission tomography (PET), and/or magnetic resonance imaging (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.

After completion of study treatment, patients are followed up every 12 weeks for 2 year and then every 24 weeks for up to 5 years.


  1. Patients must have histologically confirmed malignancy that is metastatic or unresectable
  2. 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 for study chair review: histology, nature of prior therapy (therapies) and indication for prior PD-(L)1 therapy
  3. 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
  4. Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  5. Life expectancy of greater than 12 weeks
  6. Leukocytes >= 2,000/mcL (within 28 days of treatment initiation)
  7. Absolute neutrophil count >= 1,500/mcL (within 28 days of treatment initiation)
  8. Platelets >= 100,000/mcL (within 28 days of treatment initiation)
  9. Hemoglobin >= 9 g/dL OR >= 5.6 mmol/L (within 28 days of treatment initiation)
  10. 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)
  11. 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)
  12. 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
  13. International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as (PT) or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 28 days of treatment initiation)
  14. Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as prothrombin time (PT) or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 28 days of treatment initiation)
  15. Willingness to undergo tumor biopsies at three timepoints: (1) pre-treatment; (2) after one week of rhIL12; and (3) after 2 cycles of pembrolizumab (MK-3475)-interleukin (IL) 12 (i.e., approximately 7 weeks from the first dose of rhIL-12) * At each timepoint, a core biopsy is preferable (although in suitable patients, punch biopsy may be substituted) ** Cytopathologist should be present to ensure adequacy of tumor biopsy sample ** At least 4 16 gauge (G) core biopsies are to be obtained and triaged * Pre-treatment biopsy can be substituted with an archival tissue sample if the sample is ** Adequate (capable of providing at least 20 unstained slides); and ** Recent (within 8 weeks of study entry); and ** Patient has not had any intervening therapy
  16. Patients must have measurable disease based on RECIST 1.1
  17. The effects of pembrolizumab (MK-3475) and/or rIL-12 on the developing human fetus are unknown; for this reason, 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; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year * Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately * Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of pembrolizumab (MK-3475) and/or rhIL-12 administration
  18. Ability to understand and the willingness to sign a written informed consent document
  19. Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements: * They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective * They must have an undetectable viral load * They must have a CD4 count of greater than 250 cells/mcL * They must not be receiving prophylactic therapy for an opportunistic infection

Treatment Sites in Georgia

Emory Saint Joseph's Hospital

5665 Peachtree Dunwoody Road NE
Atlanta, GA 30342

Emory University Hospital - Midtown

550 Peachtree Street NE
Atlanta, GA 30308

Winship Cancer Institute of Emory University

1365 Clifton Road NE
Building C
Atlanta, GA 30322

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.
Georgia CORE


Advancing Cancer Care through Partnerships and Innovation

Georgia CORE is a statewide nonprofit that leverages partnerships and innovation to attract more clinical trials, increase research, and promote education and early detection to improve cancer care for Georgians in rural, urban, and suburban communities across the state.