A Phase 2 Study of MK-3475 in Patients With Metastatic Melanoma and Non-Small Cell Lung Cancer With Untreated Brain Metastases

• Biopsy proven metastatic melanoma or NSCLC as follows:

∙ Patients with metastatic melanoma must have untreated brain metastases including:

⁃ At least one cerebral metastasis that requires local intervention and is amenable to craniotomy or LITT therapy either due to symptoms, lesion size, location, edema or hemorrhage (surgical lesion). Alternatively, a patient may be eligible if a cerebral metastasis was resected or biopsied any time prior to enrollment and there is tumor tissue available for analysis.

• At least one cerebral metastasis that is at least 5 mm AND twice the MRI slice thickness, but less than 20 mm, that is asymptomatic and does not require local therapy at the time of enrollment (clinically evaluable lesion(s)). OR

‣ Patients with stage IV NSCLC with at least one cerebral metastasis that is at least 5 mm AND twice the MRI slice thickness, but less than 20 mm, that is asymptomatic and does not require local therapy at the time of enrollment (clinically evaluable lesion(s)).

• Age ≥18

• ECOG performance status \< 2

• Any number of previous treatments with the exception of previous inhibitors of PD-1, PD-L1, or PD-L2; other prior systemic therapies must have been administered at least 2 weeks before administration of MK-3475 with the exception of bevacizumab which must have been administered at least 4 weeks prior to MK-3475. Patients are not required to have had prior systemic therapy. The exception to this is patients with NSCLC who test negative for PD-L1 expression or are unevaluable for PD-L1 expression must have received prior platinum-based chemotherapy for entry into Cohort 2. Note: Ipilimumab treatment should have been administered at least 4 weeks prior to the start of MK-3475.

• Life expectancy of at least 3 months

• A history of previously treated brain metastases is allowed, provided that at least 14 days have lapsed between radiation and initiation of MK-3475. Any lesion present at the time of WBRT or included in the stereotactic radiotherapy field (or within 2mm of the treated lesion) will NOT be considered evaluable unless it is new or documented to have progressed since treatment.

• PD-L1 expression in tumor tissue from any site is required for patients with NSCLC for entry into Cohort 1. Tumor tissue must be obtained after the last systemic therapy. PD-L1 expression will be analyzed by a Merck assay. For NSCLC Cohort 2, patients may test PD-L1 negative or may be unevaluable for PD-L1 expression (i.e. insufficient tumor tissue). PD-L1 expression is not required for patients with melanoma, but melanoma patients are required to submit an extra-cerebral specimen for analysis, unless it is not feasible to obtain one.

• Patients must have normal organ and marrow function as defined per protocol.

• For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of MK-3475.

⁃ For men with female partners of childbearing potential, agreement to use a latex condom, and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of MK-3475.

⁃ Negative serum or urine pregnancy test within 72 hours of commencement of treatment in premenopausal women.

⁃ Patients must have the ability to understand and the willingness to sign a written informed consent document.