Colitis, Hepatitis, Melanoma (Skin Cancer)
Conditions
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
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.
Interventions
DRUGmethoxsalen
Sterile solution used in conjunction with CELLEX ECP
Methoxsalen is used in conjunction with the CELLEX ECP
DRUGVedolizumab
Vedolizumab will be administered intravenously
DRUGInfliximab
Infliximab will be administered intravenously
DRUGMycophenolate Mofetil (MMF)
Mycophenolate Mofetil will be administered orally or intravenously
DRUGAzathioprine
Azathioprine will be administered orally or intravenously
Sponsors
Therakos LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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) | Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of irAE response | Week 64 | Time from the start of irAE response to either the relapse of irAE (if relapse occurs), or a censoring event. |
| 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) | — |
| Cumulative Systemic Corticosteroid Exposure From Randomization to Week 12 | Up to Week 12 | — |
| Peak Dose of Systemic Corticosteroid Exposure From Randomization to Week 12 | Up to Week 12 | — |
| Proportion of Participants who Completely Discontinue Systemic Corticosteroid Treatment Until Week 12 | Week 12 | — |
| Time to Complete Discontinuation of Systemic Corticosteroids for at Least 1 Week | 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 | Week 64 | — |
| Proportion of Participants With at Least one irAE who Achieve Response (as Defined per ASCO Criteria) at 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 | Week 12 | — |
Contacts
CONTACTTherakos TKS2001 Study Team
STUDY_DIRECTORIsabelle T Seemann, Ph.D
Therakos LLC
Outcome results
None listed