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

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.

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.