PHOENIX-ECP- Extracorporeal Photopheresis for Immune-related Colitis and/or Hepatitis in Advanced Melanoma With Inadequate Response to Steroid Exposure (PHOENIX-ECP)

May 27, 2026 updated by: Therakos LLC

PHOENIX- A Phase 2, Randomized, Controlled, Open-label, Multicenter Study to Evaluate the Efficacy and Safety/Tolerability of Extracorporeal Photopheresis (ECP) Versus Best Available Therapy (BAT) for the Treatment of Immune-related Colitis or Hepatitis With Inadequate Response to Corticosteroids in Participants With Unresectable or Metastatic Melanoma Treated With Immune Checkpoint Inhibitors (ICI)

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy in which the photoactivating agent methoxsalen (also known as UVADEX) is used in combination with ultraviolet A (UVA) light.

Immune checkpoint inhibitor therapy is widely used for the treatment of several cancers, including melanoma. However, a common immune-related adverse event associated with this therapy is Immune-related colitis or hepatitis. Corticosteroids are typically the first-line treatment for this condition, but some participants do not respond adequately.

The purpose of this study is to evaluate the efficacy of ECP in the treatment of immune-related (ir)-colitis and ir-hepatitis with inadequate response to corticosteroids, and to compare its efficacy to other second-line immunosuppressant therapies. The ECP procedure in this study is performed using the CELLEX® device, a fully closed-loop extracorporeal blood circulation device. The CELLEX device is used in conjunction with methoxsalen.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

112

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Participants diagnosed with unresectable or metastatic melanoma ( Stage III and Stage IV) received ICI treatment (e.g., anti-PD-1, anti-PD-L1, anti-LAG-3, anti-CTLA-4 antibody, as ICI monotherapy or ICI combination therapy) and ICI paused or discontinued because of the development of ir-colitis or ir-hepatitis.
  2. Participants diagnosed with ir-colitis and/or ir-hepatitis with a severity of Grade 2 or higher, based on ASCO Guidelines (
  3. Participants with endoscopic evidence of ir-colitis
  4. Participants with inadequate response to corticosteroids, as defined per protocol
  5. Participants who have Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.

Exclusion Criteria:

  1. Presence of irAEs in addition to and other than ir-colitis and/or ir-hepatitis, with a higher severity grade than the irAE for inclusion (ir-colitis/ir-hepatitis) based on ASCO guidelines.
  2. Participant has a diagnosis of uveal melanoma as the sole melanoma subtype
  3. Treatment of ir-colitis or ir-hepatitis with any systemic therapy other than corticosteroids
  4. Concurrent conditions which may require treatment with high dose corticosteroid (> 1 milligram per kilogram per day [mg/kg/day]) and interfere with the corticosteroid tapering schedule recommended by the protocol.
  5. Pre-existing liver disease
  6. Active alcohol use disorder
  7. Concomitant treatment with any chemotherapy or targeted therapy for the treatment of unresectable or metastatic melanoma.
  8. Use of any investigational agent within 5 half-lives of the investigational agent prior to randomization.
  9. Contraindications or known allergic reaction to any of study intervention and/or procedures
  10. Participants unable to tolerate the fluid shift associated with the ECP procedure.
  11. Positive result for active or previous viral infections: covid-19, hepatitis B/C, CMV, EBV, adenovirus
  12. History of previous or concurrent malignancies within the last 3 years, other than unresectable or metastatic melanoma.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Methoxsalen in Conjunction with Extracorporeal Photopheresis System (ECP)
Participants will receive methoxsalen, in conjunction with ECP
Drug: methoxsalen
Sterile solution used in conjunction with CELLEX ECP
Other Names:
  • UVADEX
Device: Extracorporeal photopheresis (ECP)
Methoxsalen is used in conjunction with the CELLEX ECP
Other Names:
  • CELLEX
Active Comparator: Best Available Therapy (BAT)
Participants with ir-colitis will receive either Infliximab or Vedolizumab as per the investigator's choice. Participants with ir-hepatitis will receive Mycophenolate Mofetil (MMF) or Azathioprine as per the investigator's choice.
Drug: Vedolizumab
Vedolizumab will be administered intravenously
Drug: Infliximab
Infliximab will be administered intravenously
Drug: Mycophenolate Mofetil (MMF)
Mycophenolate Mofetil will be administered orally or intravenously
Drug: Azathioprine
Azathioprine will be administered orally or intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of Participants Who are in Steroid-free response at Week 12 for the Randomized Immune-related Adverse Event (irAE) (ir-colitis or ir-hepatitis)
Time Frame: Week 12
Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of irAE response
Time Frame: Week 64
Time from the start of irAE response to either the relapse of irAE (if relapse occurs), or a censoring event.
Week 64
Progression Free Survival (PFS) for Melanoma
Time Frame: Week 64
Week 64
Overall Survival (OS)
Time Frame: Week 64
Week 64
Proportion of Participants With at Least Stable Disease as Assessed by RECIST 1.1 at Week 12 and During Follow-up
Time Frame: Week 12 and Week 64
Week 12 and Week 64
Proportion of Participants with Treatment-Emergent Adverse Event (TEAEs) per Common Toxicity Criteria for Adverse Events (CTCAE) v5.0
Time Frame: From first dose of the study drug up to end of study (up to Week 64)
From first dose of the study drug up to end of study (up to Week 64)
Cumulative Systemic Corticosteroid Exposure From Randomization to Week 12
Time Frame: Up to Week 12
Up to Week 12
Peak Dose of Systemic Corticosteroid Exposure From Randomization to Week 12
Time Frame: Up to Week 12
Up to Week 12
Proportion of Participants who Completely Discontinue Systemic Corticosteroid Treatment Until Week 12
Time Frame: Week 12
Week 12
Time to Complete Discontinuation of Systemic Corticosteroids for at Least 1 Week
Time Frame: From screening up to the first documentation of the discontinuation of systemic corticosteroid (up to Week 64)
From screening up to the first documentation of the discontinuation of systemic corticosteroid (up to Week 64)
Time to First Response of Randomized irAE Based on ASCO Criteria
Time Frame: Week 64
Week 64
Proportion of Participants With at Least one irAE who Achieve Response (as Defined per ASCO Criteria) at Week 12
Time Frame: Week 12
Week 12
Proportion of Participants With at Least One irAE That Resolves Completely (as per CTCAE v5.0) and Remains Resolved Until Week 12
Time Frame: Week 12
Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Therakos LLC

Investigators

  • Study Director: Isabelle T Seemann, Ph.D, Therakos LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

May 19, 2026

First Submitted That Met QC Criteria

May 27, 2026

First Posted (Actual)

June 2, 2026

Study Record Updates

Last Update Posted (Actual)

June 2, 2026

Last Update Submitted That Met QC Criteria

May 27, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TKS2001

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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