IL-17阻断以减少免疫相关不良事件（REPLAY） (REPLAY)

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