IMmune checkPoint Inhibitor Related gonAdal toxiCiTy in Premenopausal Women and Men With Melanoma

Inclusion Criteria:

Patients will be eligible for inclusion in this trial if all the following criteria apply:

1. Patient has provided written informed consent using the IMPACT Patient Informationand Consent form (PICF)

2. Diagnosis of melanoma (Stage II, III or IV) in the de novo or recurrent setting

3. Has a life expectancy of greater than or equal to 1 year

4. Planned to receive ICI treatment, either in the neoadjuvant, adjuvant or metastaticsetting, including as:

• Monotherapy

• Combination therapy For cohort 1: premenopausal women with melanoma

5. Age greater than or equal to 18 and less than or equal to 45 years at the time ofsigning consent

6. Patient is premenopausal (defined as baseline FSH within the premenopausal range perlocal laboratory at registration). Women on hormonal contraception who have anabnormal FSH level, will be included if their AMH level is greater than or equal to 1.0 pmol/L at registration

7. AMH level greater than or equal to 1.0 pmol/L at registration For Cohort 2: men with melanoma

8. Age greater than or equal to 18 and less than or equal to 60 years at the time ofsigning consent

9. Fasting morning total testosterone, LH and FSH within the normal range (per locallaboratory) at the time registration

Exclusion Criteria:

Patients will not be eligible for inclusion in this trial if any of the following criteria apply:

1. Previous removal of both ovaries (females) or previous removal of both testes orprevious vasectomy (males)

2. Planned for or previously had pelvic radiotherapy

3. Any medications within the prior 6 months known to disrupt the hypothalamicpituitary gonadal axis, e.g., GnRH agonists or antagonists, selective estrogenreceptor modulators (SERMs), aromatase inhibitors, testosterone, anabolic steroids,etc.

4. Previous or concurrent alkylating or platinum-based chemotherapy within the last 2years

5. Previous use of ICI

6. History of hypogonadism

7. Presence of any psychological, social, geographical, or other condition for which,in the opinion of the site Investigator, participation would not be in the bestinterest of the patient (e.g., compromise the well-being) or that could prevent,limit, or confound the protocol-specified assessments