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

Inclusion Criteria

• Adults >18 years of age 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 standard of care therapy.
• ECOG (Eastern Cooperative Oncology Group) performance status score of 0 - 2 (Appendix 1).
• 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.
• 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

• Liver function tests meeting one of the following criteria:
• AST and ALT 2.5 x ULN
• Serum bilirubin ULN in patients with Gilbert's syndrome.
• INR and aPTT 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 (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 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.
• 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, imiprami