Epacadostat, Toll-Like Receptor 9 Agonist SD-101, and Radiation Therapy in Treating Participants with Advanced, Metastatic, or Refractory Solid Tumors or Lymphoma

Status: Active


This phase I / II trial studies the side effects and best dose of epacadostat when given together with toll-like receptor 9 agonist SD-101 and radiation therapy work in treating participants with solid tumors or lymphoma that has spread to other places in the body or does not respond to treatment. Epacadostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as toll-like receptor 9 agonist SD-101, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving epacadostat, toll-like receptor 9 agonist SD-101, and radiation therapy may work better in treating participants with solid tumors or lymphoma.

Eligibility Criteria

Inclusion Criteria

  • Adults with histologically proven solid malignancy, high-grade lymphoma or low-grade lymphoma
  • Patients with incurable, advanced or metastatic disease refractory to at least one previous line of therapy
  • ECOG (Eastern Cooperative Oncology Group) performance status score of 0 – 2
  • Presence of a candidate treatment lesion (subcutaneous, nodal, or visceral) accessible and safe for radiotherapy and serial intralesional injections as specified by the protocol
  • Presence of at least one target lesion (distinct from treatment lesion and outside of treatment lesion radiation field) evaluable for response by irRECIST
  • 14 day wash-out period from any previous chemotherapy, targeted therapy or radiotherapy, 21 day washout period from previous immunotherapy
  • Life expectancy >= 6 months
  • Absolute neutrophil count (ANC) > 1500 cells/ul (obtained within 14 days of the first study treatment)
  • White blood cell (WBC) count > 2500/uL (obtained within 14 days of the first study treatment)
  • Platelet count > 50,000/uL (obtained within 14 days of the first study treatment)
  • Hemoglobin > 9 g/dL (obtained within 14 days of the first study treatment)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN) with alkaline phosphatase =< 2.5 x ULN OR
  • AST and ALT =< 1.5 x ULN, with alkaline phosphatase > 2.5 x ULN
  • Serum bilirubin =< 1.0 x ULN
  • Direct bilirubin (bili) =< 40% if total bili > ULN in patients with Gilbert’s syndrome
  • Institutional normalized ratio (INR) and partial thromboplastin time (aPTT) < 1.5 x ULN
  • Serum creatinine (Cr) =< 1.5 X ULN or creatinine clearance (CrCl) >= 50 ml/min
  • No active auto-immune disease and not on therapy for auto-immune disease. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible. Patients who have adrenal insufficiency and hypophysitis from prior immunotherapy if they are on stable medical replacement doses are eligible
  • No other active malignancy
  • Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible
  • For female patients of childbearing potential and male patients with partners of childbearing potential agreement (by patient and/or partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate [< 1% per year] when used consistently and correctly) and to continue its use for 6 months after trial completion
  • Signed informed consent
  • At least 9 months from stem cell transplant with no active graft versus host disease
  • Ability to comply with the protocol

Exclusion Criteria

  • Uncontrolled concomitant disease that in the opinion of the investigator would interfere with the patient’s safety or compliance on trial
  • Significant cardiovascular disease (New York Heart Associate [NYHA] class II or greater); myocardial infarction within 3 month prior to randomization, unstable arrhythmias, unstable angina or a patient with a known LVEF (left ventricular ejection fraction) < 40%
  • Severe infection that in the opinion of the investigator would interfere with the patient's safety or compliance on trial within 2 weeks prior to enrollment. Oral or IV antibiotics within 2 weeks or 5 half-lives prior to enrollment
  • Active tuberculosis
  • History of severe autoimmune disease that in the opinion of the investigator would interfere with patient safety or compliance on trial
  • Positive for human immunodeficiency virus (HIV), hepatitis B (hepatitis B surface antigen [HBsAg] reactive), or hepatitis C virus (hepatitis C virus ribonucleic acid [HCV RNA] [qualitative] is detected)
  • Previous treatment with epacadostat, SD-101, or any other IDO inhibitor or CpG molecule
  • Treatment with systemic corticosteroids or other systemic immunosuppressive medications within past 4 weeks or 5 half-lives whichever is shorter. Use of inhaled or topical steroids or systemic corticosteroids < 10 mg/day of prednisone (or equivalent) is permitted
  • Pregnant and/or lactating women
  • Evidence of active interstitial lung disease or active non-infectious pneumonitis
  • Receipt of live attenuated vaccine within 30 days before the first dose of study treatment
  • Use of any UGT1A9 inhibitor while on active study treatment, including the following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid
  • Known allergy or reaction to any component of either study drug formulation
  • Subjects receiving monoamine oxidase inhibitors (MAOIs) or drug which has significant MAOI activity (meperidine, linezolid, methylene blue) from 21 days prior to day 1 through 2 weeks after the final dose of epacadostat has been administered
  • Any history of serotonin syndrome (SS) after receiving serotonergic drugs
  • Known contraindications to radiotherapy including but not limited to radiation sensitivity syndromes such as xeroderma pigmentosum and ataxia telangiectasia mutated

Locations & Contacts


University of California Davis Comprehensive Cancer Center
Status: Active
Contact: Arta Monir Monjazeb
Phone: 916-734-8252
Email: ammonjazeb@ucdavis.edu

Trial Objectives and Outline


I. To determine the maximum tolerated dose (MTD) of epacadostat that can be given with radiotherapy and intralesional toll-like receptor 9 agonist SD-101 (SD-101) immunotherapy (ERS: epacadostat + radiotherapy + intralesional SD-101). (Phase I)

II. To characterize the safety profile of this regimen using CTCAE v4.03 (Common Toxicity Criteria for Adverse Events version 4.03). (Phase II)


I. To provide efficacy data for ERS as determine by abscopal response rate (defined as objective response rate at unirradiated sites) using immune related Response Evaluation Criteria in Solid Tumors (RECIST) (irRECIST) and disease control rate (DCR) defined as complete response (CR) + partial response (PR) + stable disease (SD).

II. To determine treatment tolerability.


I. To provide preliminary data on the objective response rate (ORR), progression free survival (PFS), and overall survival (OS) for ERS therapy using irRECIST and RECIST1.1 criteria.

II. To analyze serial blood samples for serum cytokine and tryptophan/kynurenine levels, and to quantify the number, function, and gene expression of circulating immune cell subsets.

III. To evaluate serial tumor tissue biopsies for tumor infiltrating immune cell subsets, expression of immune regulatory proteins including IDO and PD-L1, gene expression signatures, and mutational load.

IV. To evaluate pre-treatment stool samples for microbiome signatures.

V. To discover biomarkers of response from the data obtained in secondary objectives and above exploratory objectives.

OUTLINE: This is a phase I, dose-escalation study of epacadostat followed by a phase II study.

Participants receive epacadostat orally (PO) twice daily (BID), undergo radiation therapy 12-96 hours apart during week 1, and receive TLR9 agonist SD-101 intratumorally (IT) on days 1, 8, 15, 22, and 29. Treatment continues in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, participants are followed up at 30 days and then every 3 months.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type


Lead Organization

Lead Organization
University of California Davis Comprehensive Cancer Center

Principal Investigator
Arta Monir Monjazeb

Trial IDs

Primary ID UCDCC#271
Secondary IDs NCI-2018-01038
Clinicaltrials.gov ID NCT03322384