The study Checkmate 915 is now open in the UK.  There are a number of centres running this study.

Key Inclusion Criteria Checkmate 915 Study

1. At least 15 years of age
◦ except where local regulations and/or institutional policies impose the age of ≥18 years of age
◦ For <18 years children participating in the trial, note that they will have to consent 2 times (at the time of the entry in the study and when they turn 18 years, they have to re-consent)
2. ECOG PSS: 0 or 1
3. No prior anti-cancer therapy for their melanoma with the following exceptions:
◦ Surgery for the melanoma lesions
◦ Adjuvant radiation therapy (RT) after neurosurgical resection for CNS lesions
◦ Prior adjuvant interferon if completed ≥ 6 months prior to randomization
4. Either Stage III b/c/d or Stage IV AJCC 8th edition and have histologically confirmed melanoma completely surgically resected. Participants must have been surgically rendered free of disease with negative margins on resected specimens.
Definition of Stage III melanoma (IIIb or IIIc or IIId) as per AJCC 8th edition
Patients who only have nodal disease based on a positive SLN biopsy are eligible for inclusion if their primary melanoma is between 1-2mm with ulceration or if their primary lesion is >2mm with or without ulceration.
IIIb
T0 + N1b, N1c
N1b (one clinically detected tumor involved node) or N1c (in-transit, satellite, and/or microsatellite metastases in the absence of tumor-involved nodes)
T1 a/b – T2a + N1b/c or N2b:
T1 a/b (< 0.8mm-1mm with or without ulceration) or T2a (1-2mm without ulceration)
+
N1b/c (one clinically detected tumor involved node or in-transit, satellite, and/or microsatellite metastases in the absence of tumor-involved nodes) or N2b (Two or three tumor involved lymph nodes where at least one lymph node was clinically detected)
T2b/T3a + N1a-N2b

T2b (1-2mm with ulceration) or T3a (2-4mm without ulceration)
+
N1a/b/c (One tumor-involved node or in-transit, satellite, and/or microsatellite metastases with no tumor-involved nodes) or N2a (two or three involved lymph nodes detected by sentinel lymph node biopsy) or N2b (two or three involved lymph nodes where at least one was clinically detected)
IIIc
T0 + N2b or N2c or N3b or N3c
N2b (two or three involved lymph nodes where at least one was clinically detected) or N2c (one lymph node detected by SLNB or clinically detected in the presence of in-transit, satellite, and/or microsatellite metastases) or N3b (Four or more, at least one of which was clinically detected, or presence any number of matted nodes) or N3c (Two or more clinically occult or clinically detected, and/or presence any number of matted nodes in the presence of microsatellite/satellite/in-transit metastases.)
T1a-T3a + N2c or N3a/b/c
T1a/b (≤ 1mm with or without ulceration) or T2a/b (1-2mm with or without ulceration) or T3a (2-4mm without ulceration)
+
N2c (one lymph node detected by SLNB or clinically detected in the presence of in-transit, satellite, and/or microsatellite metastases) or N3a/b/c (Four or more tumor-involved nodes or in-transit, satellite, or microsatellite metastases with two or more tumor-involved, nodes, or any number of matted nodes with or without intransit, satellite, and/or microsatellite metastases)
T3b/T4a + any N stage ≥ N1
T3b (2-4mm with ulceration) or T4a (>4mm without ulceration)
+
N1 (One tumor-involved node or in-transit, satellite, and/or microsatellite metastases with no tumor-involved nodes) or N2 (Two or three tumor-involved nodes or in-transit, satellite, and/or microsatellite metastases with one tumor-involved node) or N3 (Four or more tumor-involved nodes or in-transit, satellite, or microsatellite metastases with two or more tumor-involved nodes, or any number of matted nodes with or without intransit, satellite, and/or microsatellite metastases)
T4b + N1a/b/c – N2 a/b/c
T4b (> 4mm with ulceration)
+
N1 (One tumor-involved node or in-transit, satellite, and/or microsatellite metastases with no tumor-involved nodes) or N2 (Two or three tumor-involved nodes or in-transit, satellite, and/or microsatellite metastases with one tumor-involved node).
IIID
T4b + N3a/b/c
t4b (> 4mm with ulceration)
+
N3a/b/c (Four or more tumor-involved nodes or in-transit, satellite, or microsatellite metastases with two or more tumor-involved nodes, or any number of matted nodes with or without intransit, satellite, and/or microsatellite metastases)
5. Documentation of negative margins must be available as follows:
◦ Stage III melanoma (IIIb or IIIc or IIId) Participants must have pathological evidence of regional metastases, regional lymph node and/or microsatellite/satellite/in-transit metastases. The pathology report must be reviewed, signed and dated by the investigator
◦ Stage IV melanoma with CNS metastases The pathology report confirming negative margins must be reviewed, dated, and signed by the investigator prior to randomization.

◦ Stage IV melanoma without CNS metastases For CNS lesion(s), documentation indicating that there has been complete resection of CNS lesion(s) will suffice as confirmation of negative margins

 

6. In patients where malignant cells have been found during SLN biopsy complete sentinel lymph node dissections is required even if there are no clinically detectable nodes on imaging
7. Tumor tissue from the resected site of disease must be provided for biomarker analyses: a block or a minimum of 15 slides is required
8. Subjects must have quantifiable PD-L1 expression (< 1%, 1% – <5%, ≥ 5%) or be classified as PD-L1 indeterminate (PD-L1 expression will be performed by BMS)
9. Complete resection must be performed within 12 weeks prior to randomization
10. Disease-free status documented by a complete physical examination and imaging studies within 4 weeks prior to randomization.
◦ For Stage IIIb/c/d and Stage IV disease without resected CNS metastases:
• imaging must include CT or MRI scans of the chest, neck, abdomen, pelvis and all known sites of resected disease
• brain magnetic resonance (MRI) or CT (brain CT allowable if MRI is contraindicated or if there is no known history of resected brain lesions)
◦ Stage IV with resected CNS metastases
• imaging must include CT or MRI scans of the chest, neck, abdomen, pelvis and all known sites of resected disease
• brain magnetic resonance (MRI) or CT (brain CT allowable if MRI is contraindicated)
11. Prior surgery must be completed as follows:
◦ Surgery that required anesthesia must be completed at least 4 weeks before drug administration.
◦ Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration.
12. Patients with equivocal lymph nodes (≥ 10 mm and < 15 mm in a short axis) within 4 weeks of randomisation may be eligible. The following applies to these participants:
◦ Where feasible a biopsy should be undertaken to confirm the absence of malignancy
◦ If a biopsy is not feasible the following are options:
Two sequential CT or MRI scans, no more than 4 weeks apart, showing no progressive and measureable disease
Or
A PET/CT demonstrating no FDG uptake
13. In participants with resected CNS metastases with or without adjuvant radiotherapy the following applies:
◦ Participants must be without MRI evidence of recurrence for at least 4 weeks after treatment i.e. Surgery and/or radiotherapy
◦ Participants must be off immunosuppressive doses of systemic steroids (≥ 10mg/day of prednisone or equivalent) for at least 14 days prior to study drug administration
◦ Participants must have returned to neurologic baseline post-operatively.
Key Exclusion Criteria
1. Subjects < 40 kg

2. History of uveal melanoma

3. Participants with active, known, or suspected autoimmune disease with the following exceptions:
◦ type I diabetes mellitus
◦ hypothyroidism only requiring hormone replacement
◦ skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment
◦ conditions not expected to recur in the absence of an external trigger

4. Participants with a condition requiring systemic treatment with either corticosteroids (≥ 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of randomization. The following exceptions apply:
◦ Inhaled or topical steroids

◦ adrenal replacement steroid doses > 10 mg daily prednisone or equivalent, are permitted in the absence of active autoimmune disease

5. Participants with previous non-melanoma malignancies are excluded unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated to be required during the study period. Exceptions include (but are not limited to):
◦ non-melanoma skin cancers
◦ In situ cancers such as bladder cancer, gastric cancer, colon cancers, cervical cancers/dysplasia ,breast carcinoma