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

NCT07619898 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: TKS2001
• Study Type: interventional
• Target: 112
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Colitis; Hepatitis; Melanoma (Skin Cancer)

Keywords

Melanoma; Immune-related adverse events; Immune-related colitis; Immune checkpoint inhibitor toxicity; Checkpoint inhibitor-induced colitis; Checkpoint inhibitor-induced hepatitis; Metastatic melanoma; Unresectable melanoma; Immune checkpoint Inhibitors; Extracorporeal photopheresis; ECP; UVADEX; Device; Methoxsalen; Steroid-refractory; Corticosteroid refractory; Phase 2 clinical trial; Randomized controlled trial; Cellex; 8-Mop; Colitis; Ir-AE; Ir-AE Colitis; Ir-AE Hepatitis

Outcome Measures

Primary Outcomes (1)

• 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)

  Week 12

Secondary Outcomes (12)

• Duration of irAE response

  Week 64

• Progression Free Survival (PFS) for Melanoma

  Week 64

• Overall Survival (OS)

  Week 64

• Proportion of Participants With at Least Stable Disease as Assessed by RECIST 1.1 at Week 12 and During Follow-up

  Week 12 and Week 64

• Proportion of Participants with Treatment-Emergent Adverse Event (TEAEs) per Common Toxicity Criteria for Adverse Events (CTCAE) v5.0

  From first dose of the study drug up to end of study (up to Week 64)

Study Arms (2)

Methoxsalen in Conjunction with Extracorporeal Photopheresis System (ECP)

EXPERIMENTAL

Participants will receive methoxsalen, in conjunction with ECP

Drug: methoxsalen; Device: Extracorporeal photopheresis (ECP)

Best Available Therapy (BAT)

ACTIVE COMPARATOR

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; Drug: Infliximab; Drug: Mycophenolate Mofetil (MMF); Drug: Azathioprine

Interventions

methoxsalen DRUG

Sterile solution used in conjunction with CELLEX ECP

Also known as: UVADEX

Methoxsalen in Conjunction with Extracorporeal Photopheresis System (ECP)

Extracorporeal photopheresis (ECP) DEVICE

Methoxsalen is used in conjunction with the CELLEX ECP

Also known as: CELLEX

Methoxsalen in Conjunction with Extracorporeal Photopheresis System (ECP)

Vedolizumab DRUG

Vedolizumab will be administered intravenously

Best Available Therapy (BAT)

Infliximab DRUG

Infliximab will be administered intravenously

Best Available Therapy (BAT)

Mycophenolate Mofetil (MMF) DRUG

Mycophenolate Mofetil will be administered orally or intravenously

Best Available Therapy (BAT)

Azathioprine DRUG

Azathioprine will be administered orally or intravenously

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 ( 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.
• Participants diagnosed with ir-colitis and/or ir-hepatitis with a severity of Grade 2 or higher, based on ASCO Guidelines (
• Participants with endoscopic evidence of ir-colitis
• Participants with inadequate response to corticosteroids, as defined per protocol
• Participants who have Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.

You may not qualify if:

• Participant has a diagnosis of uveal melanoma as the sole melanoma subtype
• Treatment of ir-colitis or ir-hepatitis with any systemic therapy other than corticosteroids
• 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.
• Pre-existing liver disease
• Active alcohol use disorder
• Concomitant treatment with any chemotherapy or targeted therapy for the treatment of unresectable or metastatic melanoma.
• Use of any investigational agent within 5 half-lives of the investigational agent prior to randomization.
• Contraindications or known allergic reaction to any of study intervention and/or procedures
• Participants unable to tolerate the fluid shift associated with the ECP procedure.
• Positive result for active or previous viral infections: covid-19, hepatitis B/C, CMV, EBV, adenovirus
• History of previous or concurrent malignancies within the last 3 years, other than unresectable or metastatic melanoma.

Sponsors & Collaborators

• Therakos LLC: lead

MeSH Terms

Conditions

Colitis; Hepatitis; Melanoma

Interventions

Methoxsalen; Photopheresis; vedolizumab; Infliximab; Mycophenolic Acid; Azathioprine

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Liver Diseases; 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

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; PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Isabelle T Seemann, Ph.D

  Therakos LLC

  STUDY DIRECTOR

Central Study Contacts

Therakos TKS2001 Study Team

CONTACT

855-512-3327; Clinicaltrials@therakos.com

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: May 19, 2026
• First Posted: June 2, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share