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

NCT03322384 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 1057229UCDCC#271
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Checkpoint blockade immunotherapy has revolutionized the management of a variety of advanced malignancies. Monoclonal antibodies targeting the PD-1 / PD-L1 interaction have received FDA approvals for non-small cell lung cancer, melanoma, Merkel cell carcinoma, renal cell carcinoma, hepatocellular, squamous cell carcinoma of the head and neck, microsatellite instability high colorectal carcinoma, urothelial carcinoma, and classical Hodgkin's lymphoma. Despite the promising evidence for deep and durable responses with these agents, the majority of patients either fail to respond or develop resistance to treatment. Thus, there is interested in developing alternative immunotherapeutic strategies. The investigators hypothesize that a novel immunotherapeutic combination of radiotherapy (RT) with intralesional CpG and indolamine-2,3-dioxygenase blockade may offer significant clinical benefit to patients and proposing a microtrial testing this combination for advanced/refractory solid tumors and lymphoma.

Conditions

Advanced Solid Tumors; Lymphoma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  To determine the maximum tolerated dose (MTD) of epacadostat that can be given with radiotherapy and intralesional SD-101 immunotherapy for the phase I portion of the study. The MTD will be determined using a standard 3+3 design. Patients will be monitored weekly during a 30-day dose-limiting toxicity (DLT) period. MTD can be defined as The maximum dose at which \<2 of 6 patients experienced a DLT.

  Up to 30 days of treatment

• Incidence of Related Adverse Events [Safety and Tolerability]

  To characterize the safety profile of this regimen using CTCAE v4.03 (Common Toxicity Criteria for Adverse Events version 4.03) in the phase II expansion . The expansion phase (phase II) will be conducted using the MTD defined as the highest dose at which no more than one of six patients develops a DLT or Dose Level 1 if the MTD is not reached. Patients will be monitored every week during the first 30 days of study and then monthly thereafter up to a period of 1 year.

  Through study completion, an average of one year

Secondary Outcomes (1)

• Abscopal Response Rate

  Through study completion, an average of one year

Study Arms (1)

Experimental

EXPERIMENTAL

All patients will begin epacadostat on day 1 of radiotherapy, which will consist of three threatments over one week. Epacadostat will continue until disease progression or intolerance occurs. On days 1, 8, 15, 22, 29, intralesional injectinons of SD101 will be given to patients.

Drug: epacadostat; Drug: SD-101; Radiation: Radiotherapy

Interventions

epacadostat DRUG

Epacadostat will be administered orally, in pill form, twice daily until disease progression.

Experimental

SD-101 DRUG

Four milligrams of SD-101 will be delivered into the treatment lesion by intralesional injection on days 1, 8, 15, 22, and 29.

Experimental

Radiotherapy RADIATION

Radiotherapy will be delivered to the treatment lesion during the first week of ERS therapy.

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 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 bili \< 40% if total bili \> ULN in patients with Gilbert's syndrome.
• INR and aPTT \< 1.5 x ULN.
• Serum Cr \< 1.5 X ULN or CrCl \> 50 ml/min.

You may not qualify if:

• 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, 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.

Sponsors & Collaborators

• University of California, Davis: lead

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Lymphoma

Interventions

epacadostat; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

• Title: Analyst
• Organization: University of California, Davis

nlogihara@ucdavis.edu

9167348053

Study Officials

• Megan Daly, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: All patients will begin epacadostat on day 1 of radiotherapy, which will consist of three threatments over one week. Epacadostat will continue until disease progression or intolerance occurs. On days 1, 8, 15, 22, 29, intralesional injectinons of SD101 will be given to patients.

Study Record Dates

• First Submitted: October 23, 2017
• First Posted: October 26, 2017
• Study Start: January 17, 2018
• Primary Completion: February 24, 2020
• Study Completion: April 8, 2020
• Last Updated: February 1, 2022
• Results First Posted: December 21, 2021

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)