Dr. Anna Spreafico
Inclusion Criteria:
1. Age ≥ 18 years at the time of screening or age of consent according to law.
2. Written informed consent and any locally required authorization (e.g., data privacy)
obtained from the subject prior to performing any protocol-related procedures,
including screening evaluations.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Must have a life expectancy of at least 12 weeks.
5. Histologically confirmed cutaneous or mucosal melanoma.
6. High risk melanoma subjects with disease staging for which adjuvant immunotherapy
has been proven to reduce the risk of relapse versus observation (disease stage: 2B,
2C, 3A, 3B, 3C, 3D, 4 fully resected).
7. Archival tumor formalin-fixed, paraffin-embedded (FFPE) specimens for correlative
biomarker studies are required (1 H&E and 10 unstained 5 microns slides). If surgery
is going to be performed after signing consent, then tumor FFPE from that surgery is
allowed.
8. Patient is a candidate for definitive treatment: including surgery, and
post-operative adjuvant immunotherapy with or without radiation for local control.
9. No detectable disease via imaging (CT scan, MRI, with or without Positron emission
tomography (PET) CT scan). Table 4.1.2-1 : Criteria for adequate organ and Marrow
function
10. Females of childbearing potential who are sexually active with a non-sterilized male
partner must use at least one highly effective method of contraception (see Section
8.1.1 for definition of females of childbearing potential and for a description of
highly effective methods of contraception) from screening to 180 days after the
final dose of study treatment. It is strongly recommended for the male partner of a
female subject to also use male condom plus spermicide throughout this period.
Cessation of contraception after this point should be discussed with a responsible
physician. Periodic abstinence, the rhythm method, and the withdrawal method are not
acceptable methods of contraception.
11. Non-sterilized male subjects who are sexually active with a female partner of
childbearing potential must use a male condom with spermicide from screening to 180
days after receipt of the final dose of study treatment. It is strongly recommended
for the female partner of a male subject to also use a highly effective method of
contraception throughout this period, as described in Section 8.1.2. In addition,
male subjects must refrain from sperm donation while on study and for 180 days after
the final dose of study treatment.
Exclusion Criteria:
1. Diagnosis of uveal melanoma.
2. Any prior systemic anticancer therapy for melanoma. Any concurrent anticancer
treatment. Concurrent use of hormonal therapy for non-cancer-related conditions
(e.g., hormone replacement therapy) is allowed.
3. Evidence of metastatic disease at surgical and radiological staging.
4. History of allogeneic organ transplantation.
5. History of allergic reactions or hypersensitivity attributed to compounds of similar
chemical or biologic composition to anti-PD-1 or anti-LAG-3 or any of their
excipients.
6. History of active primary immunodeficiency.
7. Active autoimmune or inflammatory disorders (including inflammatory bowel disease
[eg, colitis or Crohn's disease], immune related diverticulitis [prior
diverticulitis in the context of diverticulosis is allowed provided is not active],
systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome
[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis,
hypophysitis, uveitis, etc.].
The following are exceptions to this criterion:
1. Participants with vitiligo or alopecia
2. Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on
hormone replacement
3. Any chronic skin condition that does not require systemic therapy. Participants
without active disease in the last 1 year may be included but only after
consultation with the Principal Investigator
4. Participants with celiac disease controlled by diet alone
8. Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and tuberculosis testing in
line with local practice), hepatitis B (known positive Hepatitis B virus (HBV)
surface antigen [HBsAg] result), or hepatitis C (HCV). Participants with a past or
resolved HBV infection (defined as the presence of hepatitis B core antibody
[anti-HBc] and absence of HBsAg) are eligible. Participants positive for HCV
antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
Subjects with well-controlled Human Immunodeficiency Virus (HIV) are allowed.
9. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension,
clinically relevant coronary artery disease or history of myocardial infarction in
the last 4 months or high risk of uncontrolled arrhythmia, active interstitial lung
disease, serious chronic gastrointestinal conditions associated with diarrhea, or
psychiatric illness/social situations that would limit compliance with study
requirement, substantially increase risk of incurring adverse events (AEs) or
compromise the ability of the participant to give written informed consent.
10. History of another primary malignancy except for:
1. Malignancy treated with curative intent and with no known active disease ≥ 3
years before the first dose of study treatment and of low potential risk for
recurrence.
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease.
3. Adequately treated carcinoma in situ without evidence of disease.
4. Participants with a history of prostate cancer (tumor/node/metastasis stage) of
Stage ≤ T2cN0M0 without biochemical recurrence or progression and who in the
opinion of the investigator are not deemed to require active intervention
11. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 500
msecs calculated from three ECGs.
12. Prior nivolumab or relatlimab therapy.
13. Current or prior use of immunosuppressive medication within 14 days before the first
dose of study intervention. The following are exceptions to this criterion (see
Section 4.7.1.1):
1. Intranasal, inhaled, topical steroids, or local steroid injections (eg,
intra-articular injection)
2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
3. Steroids as premedication for hypersensitivity reactions (eg, CT scan
premedication)
14. Receipt of live attenuated vaccine within 30 days prior to the first dose of study
intervention. Note: Participants should not receive live vaccine whilst receiving
study intervention and up to 30 days after the last dose of study intervention.
Should the participants be deemed candidates for the Monkey pox vaccine, the case
will need to be discussed with the coordinating Principal Investigator.
15. Participation in another clinical study with an investigational product administered
in the last 28 days prior to randomization or concurrent enrollment in another
clinical study, unless the study is an observational (non-interventional) clinical
study or during the follow-up period of an interventional study.
16. Judgment by the investigator that the participant should not participate in the
study if the participant is unlikely to comply with study procedures, restrictions
and requirements.
17. For women only - currently pregnant (confirmed with positive pregnancy test) or
breastfeeding.
18. Subjects who are unable to willingly provide consent or are unable to comply with
the protocol procedures.