EPIC- Extracorporeal Photopheresis (ECP) for Immune-related Colitis (EPIC)

EPIC - A Phase 2, Randomized, Open-label, Multicenter, Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Extracorporeal Photopheresis (ECP) Versus Best Available Therapy (BAT) in Melanoma or Non-Small Cell Lung Cancer (NSCLC) Patients With Immune-related Colitis Induced by Immune Checkpoint Inhibitor Therapy Who Have Inadequate Response to Steroids

The photoactivating agent UVADEX (methoxsalen) is used in conjunction with extracorporeal photopheresis (ECP) as an immunomodulatory therapy approved for the treatment of cutaneous T-cell lymphoma. ECP involves collecting whole blood from the patient, separating white blood cells (WBCs) via centrifugation, combining them with UVADEX, and then exposing them to ultraviolet A (UVA) light. All blood components, including the treated WBCs, are then returned to the patient.

Immune Checkpoint inhibitor (ICI) therapy is used to treat different types of cancer, and one major side-effect of ICI therapy is immune-related colitis (ir-colitis). The main purpose of the study is to evaluate the efficacy of UVADEX in conjunction with ECP versus best available therapy (BAT) in participants with melanoma or NSCLC that suffer from ir-colitis with inadequate response to steroids.

Study Overview

• Status: Withdrawn
• Conditions: Immune-related Colitis
• Intervention / Treatment: Drug: Methoxsalen; Drug: Infliximab; Drug: Vedolizumab

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants diagnosed with unresectable or metastatic melanoma or unresectable, advanced or metastatic NSCLC, who received ICI treatment with agents like anti-programmed death-1 (PD-1), anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), and had shown a response to the treatment, based on having a complete response, partial response, or stable disease determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
• Participants diagnosed with ir-colitis of at least Grade 2 severity based on American Society of Clinical Oncology (ASCO) Guidelines (diarrhea with an increase of ≥4 stools more than at baseline) with other causes of diarrhea and colitis ruled out.
• Participants with endoscopy evidence of ir-colitis based on colonoscopy (modified Mayo Endoscopy Subscore of ≥2).
• Participants with inadequate response to corticosteroids, defined as no improvement in ir-colitis after at least 72 hours of corticosteroid treatment, or relapse of ir-colitis during or after corticosteroid tapering.
• Participants who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2.
• Participants who may become pregnant must have a negative serum pregnancy test, agree to use effective birth control methods during the study and for 30 days after the last treatment, and not be breastfeeding.
• Participants whose sexual partner may become pregnant, must use condoms or other effective contraception, and avoid donating blood, semen, or sperm during the study and for 90 days after the last treatment.
• Participants must agree to wear UVA-absorbing, wrap-around sunglasses and cover exposed skin or use a sunblock (sun protection factor [SPF] ≥ 15) for the 24-hour period following treatment with UVADEX, whether exposed to direct or indirect sunlight.

Exclusion Criteria:

• Presence of irAEs and other than ir-colitis, with severity grade > 2 based on ASCO guidelines.
• Treatment of ir-colitis with any systemic therapy other than corticosteroids.
• Concurrent conditions that might require treatment with corticosteroids ≥ 1 milligram per kilogram body weight per day (mg/kg BW/day) prednisone equivalent.
• Concomitant treatment with any chemotherapy or targeted therapy for malignant melanoma, NSCLC, or other cancers.
• Use of any investigational agent within 5 half-lives of the study treatment.
• Contraindications to study interventions or procedures (UVADEX, the ECP procedure, infliximab, or vedolizumab).
• Known allergic reaction to any component of the investigational agents, 8-methoxsalen (UVADEX), infliximab, or vedolizumab.
• Presence of aphakia or history of light-sensitive diseases such as lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum, or albinism.
• Inability to tolerate the fluid shift associated with the ECP procedure.
• Positive test for human immunodeficiency virus (HIV).
• Positive test for tuberculosis (blood test).
• History of prior allogeneic bone marrow or solid organ transplantation.
• Previous or current malignancies within the last 3 years, other than unresectable or metastatic melanoma or unresectable, advanced, or metastatic NSCLC treated with ICI. Exceptions include adequately treated basal or squamous cell skin cancer.

Note: Other Inclusion/Exclusion criteria also apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UVADEX in conjunction with extracorporeal photopheresis; Participants will receive UVADEX, in conjunction with ECP procedure twice weekly for four weeks and then every other week for 8 weeks during the 12-week treatment period according to the treatment schedule.	Drug: Methoxsalen; Sterile solution used in conjunction with photopheresis procedure.; Other Names: UVADEX®, 20 micrograms per milliliter (mcg/mL)
Active Comparator: Best available therapy (BAT); Participants will receive either infliximab or vedolizumab as per the investigator's choice during the 12-week treatment period.	Drug: Infliximab; Infliximab will be administered intravenously.; Other Names: REMICADE®; INFLECTRA®; IXIFI®; RENFLEXIS®; AVSOLA®; Drug: Vedolizumab; Vedolizumab will be administered intravenously.; Other Names: ENTYVIO®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants with Remission of ir-colitis at End of Treatment	Composite endpoint of remission measured by diarrhea frequency (CTCAE grade 0 or 1 at Week 12) and colonic mucosal endoscopy score (modified Mayo Score 0 or 1 at Week 13).	Week 12 (diarrhea frequency) / Week 13 (colonic mucosal endoscopy score)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Duration of Remission for ir-colitis Based on the Criteria for Diarrhea	Duration of remission is the time from when diarrhea improves until the time it comes back (if it does).	Week 64
Proportion of Participants with Complete Resolution of Diarrhea	Complete resolution of diarrhea refers to normal stool frequency.	Week 12
Proportion of Participants with Complete Resolution of Colonic Endoscopic Changes	Complete resolution of colonic endoscopic changes refers to no signs of inflammation or damage in the colon.	Week 13
Proportion of Participants with Corticosteroid-free Clinical Remission	Corticosteroid-free clinical remission is assessed based on the absence of diarrhea and daily corticosteroid dose <5 mg prednisolone or equivalent at week 12.	Week 12
Proportion of Participants with Stool Calprotectin Level <150 micrograms per gram (μg/g)		Week 26
Proportion of Participants with Complete Resolution of Other Symptoms of ir-colitis		Week 64
Time to Complete Resolution of ir-colitis Based on Common Terminology Criteria for Adverse Events (CTCAE) Criteria for Colitis		Week 64
Time to Complete Resolution of Other Specified Immune-related Adverse Events (irAEs) (other than ir-colitis)	The other specified irAEs may include pruritis, rash, inflammatory dermatitis, esophagitis, gastritis, hepatitis, pneumonitis, arthritis, myositis, polymyalgia and nephritis.	Week 64
Time to Complete Discontinuation of Systemic Corticosteroids for at least 1 Week	This is the time taken by a participant to stop using systemic corticosteroids entirely for at least one week.	Week 12
Progression Free Survival (PFS) for Melanoma and NSCLC	The approximate time from the start of treatment until the first incidence of cancer worsening or participants dying due to any cause.	Week 64
Overall Survival (OS)	The approximate time from the start of treatment until death due to any cause.	Week 64
Changes in the Nancy Score	The Nancy histological index comprises 3 histological items defining 5 grades of disease activity: Grade 0 is absence of significant histological disease; Grade 1 is chronic inflammatory infiltrate with no acute inflammatory infiltrate; Grade 2 is mildly active disease; Grade 3 is moderately active disease; and Grade 4 is severely active disease.	Week 13

Collaborators and Investigators

• Sponsor: Therakos LLC
• Investigators: Study Director: Clinical Team Leader, Therakos LLC

Study record dates

Study Major Dates

• Study Start (Estimated): December 15, 2025
• Primary Completion (Estimated): February 6, 2026
• Study Completion (Estimated): February 19, 2027

Study Registration Dates

• First Submitted: October 15, 2024
• First Submitted That Met QC Criteria: October 15, 2024
• First Posted (Actual): October 17, 2024

Study Record Updates

• Last Update Posted (Actual): December 26, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; Melanoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Carcinoma, Non-Small-Cell Lung; Melanoma; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coumarins; Benzopyrans; Heterocyclic Compounds, 3-Ring; Furocoumarins; Infliximab; Methoxsalen; vedolizumab
• Other Study ID Numbers: MNK60052002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No