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

Official title

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)

Overview

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.

Interventions

• Drug methoxsalen
  Sterile solution used in conjunction with CELLEX ECP
• Device Extracorporeal photopheresis (ECP)
  Methoxsalen is used in conjunction with the CELLEX ECP
• 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

Primary outcome measures

• 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]

Secondary outcome measures (12)

• Duration of irAE response [Time frame: Week 64]
• Progression Free Survival (PFS) for Melanoma [Time frame: Week 64]
• Overall Survival (OS) [Time frame: 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]
• 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)]
• Cumulative Systemic Corticosteroid Exposure From Randomization to Week 12 [Time frame: Up to Week 12]
• Peak Dose of Systemic Corticosteroid Exposure From Randomization to Week 12 [Time frame: Up to Week 12]
• Proportion of Participants who Completely Discontinue Systemic Corticosteroid Treatment Until Week 12 [Time frame: 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)]
• Time to First Response of Randomized irAE Based on ASCO Criteria [Time frame: 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]
• 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]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07619898 · TKS2001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗