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

NCT06646016 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: MNK60052002
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Immune-related Colitis

Keywords

Melanoma; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Total Duration of Remission for ir-colitis Based on the Criteria for Diarrhea

  Week 64

• Proportion of Participants with Complete Resolution of Diarrhea

  Week 12

• Proportion of Participants with Complete Resolution of Colonic Endoscopic Changes

  Week 13

• Proportion of Participants with Corticosteroid-free Clinical Remission

  Week 12

• Changes in the Nancy Score

  Week 13

Study Arms (2)

UVADEX in conjunction with extracorporeal photopheresis

EXPERIMENTAL

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

Best available therapy (BAT)

ACTIVE COMPARATOR

Participants will receive either infliximab or vedolizumab as per the investigator's choice during the 12-week treatment period.

Drug: Infliximab; Drug: Vedolizumab

Interventions

Methoxsalen DRUG

Sterile solution used in conjunction with photopheresis procedure.

Also known as: UVADEX®, 20 micrograms per milliliter (mcg/mL)

UVADEX in conjunction with extracorporeal photopheresis

Infliximab DRUG

Infliximab will be administered intravenously.

Also known as: REMICADE®, INFLECTRA®, IXIFI®, RENFLEXIS®, AVSOLA®

Best available therapy (BAT)

Vedolizumab DRUG

Vedolizumab will be administered intravenously.

Also known as: ENTYVIO®

Best available therapy (BAT)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Therakos LLC: lead

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung

Interventions

Methoxsalen; Infliximab; vedolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Furocoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Team Leader

  Therakos LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 17, 2024
• Study Start: December 15, 2025
• Primary Completion: February 6, 2026
• Study Completion (Estimated): February 19, 2027
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)