IL-17 Blockade to Decrease irAEs (REPLAY) (REPLAY)

A Feasibility Study Utilizing IL-17 Blockade to Decrease Risk of Immune Related Adverse Events

The primary objective of this study is to determine the safety and feasibility of administering an IL-17A (human IgG1κ) monoclonal antibody, (Secukinumab, Cosentyx®) to participants with metastatic melanoma who have previously received immune checkpoint inhibitor (ICI) therapy, experienced an immune related adverse event (colitis, hepatitis, skin rash, psoriatic arthritis) to ICI, and are re-initiating ICI therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Melanoma
• Intervention / Treatment: Drug: Secukinumab Injection

Detailed Description

Participants will receive pre-treatment (pre-ICI) with secukinumab (300mg) within 1 to 7 days prior to the initial ICI dose. Participants will then resume ICI therapy (the specific ICI agent and dose are determined by the treating physician per their standard practice). Participants will receive secukinumab weekly for the first 4 weeks, and then once every 4 weeks thereafter until grade 3 side effect occurs or ICI is discontinued.

Participants will have AE (adverse event) assessments at each study visit. Disease assessments via CT scans will be performed every 12 weeks with iRECIST/RECIST. Research blood samples and tumor tissue will be collected. All participants will be followed by phone call or medical record review for survival for up to three years. Participants who come off for reasons other than disease progression will also be followed with CT scans every 12 weeks until progression for up to two years.

• Study Type: Interventional
• Enrollment (Estimated): 4
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Emily Bolch; Email: emily.bolch@duke.edu
• Study Contact Backup: Name: April Salama, MD; Phone Number: +1 919 681 9507; Email: april.salama@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Histologically confirmed advanced metastatic melanoma
2. Participants of any gender who are at least 18 years of age on the day of signing informed consent
3. Participants must be planned or scheduled by their treating physician to receive PD-1 therapy or PD-1 plus anti LAG3 or PD-1 plus anti CTLA-4 therapy as standard of care. Patients should either be restarting the same ICI regimen which contributed to the prior toxicity or have a clinical need to escalate to doublet (combination) ICI therapy, plan for therapy should be reviewed by the PI of this study.
4. Participant (or legally acceptable representative if applicable) provides written informed consent for the trial

5. Participant must have had prior treatment with ICI therapy (either PD-1 therapy or PD-1 plus anti LAG3 or PD-1 plus anti CTLA-4 therapy as standard of care) and experienced grade 2 or higher immune-related colitis, hepatitis, or skin rash leading to treatment interruption or discontinuation or requiring steroid administration (systemic or topical).

   • Note that patients who experience more than one irAEs are eligible to participate

6. Adequate organ function as defined below. Standard of care labs drawn within 42 days prior to consent may be used for the purposes of determining eligibility.

   • Absolute Neutrophil Count (ANC) ≥ 1500/µL
   • Platelets ≥ 100,000/µL
   • Hemoglobin* ≥ 9.0 g/dL or ≥ 5.6 mmol/L *Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within the previous 2 weeks
   • AST/ALT 2.5x upper limit of normal

Exclusion Criteria:

1. Uveal melanoma
2. Any participants known to be pregnant or breastfeeding.
3. Known diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone or equivalent), or any other form of immunosuppressive therapy within 7 days prior to first research biopsy

4. Patients with symptomatic CNS metastases and/or carcinomatous meningitis

   • Patients with asymptomatic, clinically stable CNS metastases are allowed provided they do not require steroid treatment
5. History of or active (non-infectious) pneumonitis that required steroids
6. Active infection requiring systemic therapy
7. Known history of Human Immunodeficiency Virus (HIV) infection
8. Known history of Hepatitis B or known active Hepatitis C virus infection. NOTE: no testing for Hepatitis B or Hepatitis C is required
9. Known history of active TB (Bacillus Tuberculosis)
10. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with subject's participation for the full duration of the study, or make it not in the best interest of the subject to participate, in the opinion of the treating physician
11. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
12. History of allogenic tissue or solid organ transplant
13. History of active autoimmune disease requiring systemic therapy within the past 12 months, with the exception of ICI induced irAEs.
14. Has not been treated with secukinumab within the last 12 months
15. History of prior cardiac, neurologic, ocular IRAE related to ICI; history of blistering cutaneous IRAE related to ICI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Secukinumab; Participants will first undergo pre-treatment with secukinumab (300mg subcutaneously) within 1 to 7 days prior to resumption of ICI treatment. Participants will then undergo anti-PD-1 therapy, anti PD-1 plus anti LAG3 (relatlimab) or anti-PD-1 plus anti CTLA-4 therapy at the discretion of their treating physician. Participants will concurrently receive secukinumab 300mg subcutaneously weekly for the first 4 weeks of treatment and then every 4 weeks.

Drug: Secukinumab Injection; Secukinumab 300mg subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of administering an IL-17A (human IgG1κ) monoclonal antibody (secukinumab) as determined by occurrence of immune-related Adverse Events (irAEs)	Participants will be assessed for AEs at each study visit. AEs are graded by NCI-CTCAE v5.0 criteria.	Until grade 3 side effect occurs or three years, whichever comes first
Feasibility of administering an IL-17A (human IgG1κ) monoclonal antibody (secukinumab) as determined by occurrence of immune-related Adverse Events (irAEs)	Participants will be assessed for AEs at each study visit. AEs are graded by NCI-CTCAE v5.0 criteria.	Until grade 3 side effect occurs or three years, whichever comes first

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: April Salama, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 20, 2025

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; secukinumab
• Other Study ID Numbers: Pro00118701

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No