UCDCC#271: Phase I/II Trial of Epacadostat, Intralesional SD101, Radiotherapy in Patients With Lymphoma

Inclusion Criteria:

1. Adults \>18 years of age with histologically proven solid malignancy, high-grade lymphoma or low-grade lymphoma.
2. Patients with incurable, advanced or metastatic disease refractory to at least one previous line of standard of care therapy.
3. ECOG (Eastern Cooperative Oncology Group) performance status score of 0 - 2 (Appendix 1).
4. Presence of a candidate treatment lesion (subcutaneous, nodal, or visceral) accessible and safe for radiotherapy and serial intralesional injections as specified by the protocol.
5. Presence of at least one target lesion (distinct from treatment lesion and outside of treatment lesion radiation field) evaluable for response by irRECIST.
6. 14 day wash-out period from any previous chemotherapy, targeted therapy or radiotherapy, 21 day washout period from previous immunotherapy.
7. Life expectancy ≥ 6 months.
8. Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days of the first study treatment:

   o ANC \> 1500 cells/ul; WBC count \> 2500/uL; Lymphocyte count \>500/uL; Platelet count \> 100,000/uL; Hemoglobin \> 9 g/dL
9. Liver function tests meeting one of the following criteria:

   1. AST and ALT \< 2.5 x ULN with alkaline phosphatase \< 2.5 x ULN OR
   2. AST and ALT \< 1.5 x ULN, with alkaline phosphatase \> 2.5 x ULN
   3. Serum bilirubin \< 1.0 x ULN. Direct bili \< 40% if total bili \> ULN in patients with Gilbert's syndrome.
10. INR and aPTT \< 1.5 x ULN.
11. Serum Cr \< 1.5 X ULN or CrCl \> 50 ml/min.
12. 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.
13. No other active malignancy.
14. Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible.
15. 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.
16. Signed informed consent.
17. At least 9 months from stem cell transplant with no active graft versus host disease.
18. Ability to comply with the protocol.

Exclusion Criteria:

1. Uncontrolled concomitant disease that in the opinion of the investigator would interfere with the patient's safety or compliance on trial.
2. Significant cardiovascular disease (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%
3. Severe infection that in the opinion of the investigator would interfere with the patients 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.
4. Active tuberculosis
5. History of severe autoimmune disease that in the opinion of the investigator would interfere with patient safety or compliance on trial.
6. 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)
7. Previous treatment with epacadostat, SD-101, or any other IDO inhibitor or CpG molecule.
8. 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.
9. Pregnant and/or lactating women.
10. Evidence of active interstitial lung disease or active non-infectious pneumonitis
11. Receipt of live attenuated vaccine within 30 days before the first dose of study treatment.
12. Use of any UGT1A9 inhibitor while on active study treatment, including the following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid.
13. Known allergy or reaction to any component of either study drug formulation.
14. 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.
15. Any history of Serotonin Syndrome (SS) after receiving serotonergic drugs.
16. Known contraindications to radiotherapy including but not limited to radiation sensitivity syndromes such as xeroderma pigmentosum and ataxia telangiectasia mutated.