A Phase II Study of PD-1 Blockade with Pembrolizumab In Patients with Locally Advanced and Metastatic Desmoplastic Melanoma (DM)

1. Cohort A:
Cohort A: Patients must have histologically or cytologically confirmed primary
desmoplastic melanoma (see Section 12.1 for definition) that is deemed
resectable. The decision to perform surgery on patients must be based on good
clinical judgment. Eligible patients for surgical resection must have disease that,
in the judgment of the surgeon, is deemed completely resectable resulting in free
surgical margins. Patients must have residual disease after initial biopsy which
can be measurable or non-measurable disease per RECIST 1.1 (see Section
10.1). Residual disease can either be confirmed with FNA or if measurable
disease is present, no FNA needs to be obtained.OR
Cohort B:
Patients must have histologically or cytologically confirmed primary desmoplastic melanoma that is unresectable.
Patients in Cohort B must have measurable disease per RECIST 1.1.
3. Patients must not have known brain metastases unless brain metastases have been treated and patient is asymptomatic with no residual neurological dysfunction and has not received enzyme-reducing anti-epileptic drugs or corticosteroids for at least 14 days prior to registration.
4. Patients must not have received prior systemic treatment for this melanoma and must not be planning to receive concomitant other biologic therapy, radiation therapy, hormonal therapy, other chemotherapy, anti-cancer surgery or other anti-cancer therapy after registration step 2.
5. Patients must not have received non-cytotoxic agents or investigational agents or systemic corticosteroids within 14 days prior to registration.
6. Patients may have received prior surgery. All adverse events associated with prior surgery must have resolved to </= Grade 1 (per CTCAE 4.0) prior to registration.
7. >/= 18 years of age.
8. Adequate bone marrow function as evidenced by all of the following: ANC >/= 1,500/mcl; platelets >/= 50,000/mcl; and hemoglobin >/= 9 g/dL.
9. Adequate liver function as evidenced by the following: total bilirubin </= 1.5 x institutional upper limit of normal (IULN) (or </= 3.0 x IULN with Gilbert's Syndrome), and AST and ALT </= 2.5 x IULN (or < 5 x IULN for patients with known liver metastases).
10. Patients must have LDH performed within 28 days prior to registration.
11. Zubrod Performance Status </= 2
12. No history of (non-infectious) pneumonitis that required steroids or current neumonitis.
13. No active infection requiring systemic therapy.
14. No active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
15. Patients must not have received live vaccines within 42 days prior to registration.
16. Patients known to be HIV positive prior to registration are eligible if they meet the following criteria within 30 days prior to registration: stable and adequate CD4 counts (>/= 350 mm3), and serum HIV viral load of < 25,000 IU/ml. Patients must be on a stable anti-viral therapy.
17. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated in situ cancer, adequately treated Stage I or II cancer (including multiple primary melanomas) from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
18. Women of childbearing potential must have a negative urine or serum pregnancy test. Women/men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study through 120 days after the last dose of study medication.
19. Patients must have specimens available and institutions must be planning to submit for centralized pathology review and for integrated translational medicine objectives.