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

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