Phase IB Study of MK-3475 in Subjects with Select Advanced Solid Tumors

1. Have histologically or cytologically-documented, locally-advanced, or metastatic solid malignancy that has either (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the patient and treating physician. There is no limit to the number of prior treatment regimens.;2. Have one of the following advanced (unresectable and/or metastatic) solid tumor indications for which no curative therapy exist:;A1 Colon or Rectal Adenocarcinoma
A2 Anal Canal Squamous Cell Carcinoma
A3 Pancreas Adenocarcinoma
A4 Esophageal Squamous Cell Carcinoma or Adenocarcinoma (Including GE Junction)
A5 Biliary Tract Adenocarcinoma (Gallbladder and Biliary Tree but excluding Ampulla of Vater Cancers)
A6 Carcinoid Tumors
A7 Neuroendocrine Carcinomas (Well or moderately differentiated Pancreatic Neuroendocrine Tumor)
B1 ER Positive HER2 Negative Breast Cancer a
B2 Ovarian Epithelial, Fallopian Tube or Primary Peritoneal Carcinoma
B3 Endometrial Carcinoma b
B4 Cervical Squamous Cell Cancer
B5 Vulvar Squamous Cell Carcinoma
C1 Small Cell Lung Cancer
C2 Mesothelioma (Malignant Pleural Mesothelioma)
D1 Thyroid Cancer (Papillary or Follicular Subtype)
D2 Salivary Gland Carcinoma b
D3 Nasopharyngeal Carcinoma
E1 Glioblastoma Multiforme c
E2 Leiomyosarcoma
E3 Prostate Adenocarcinoma d
a Note: ER positive HER2 negative status for breast cancer cohort defined by local standards.
b Note: All carcinoma subtypes are allowed however sarcomas or mesenchymal tumors are excluded.
c Note: Glioblastoma multiforme subjects with any prior bevacizumab treatment are NOT eligible.
d Note: Subjects with prostate cancer who are currently on LHRH analogs are eligible for this study and may continue to take the LHRH analogs while participating in this study.;3. Have provided tissue for biomarker analysis from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated (tumors progressing in a prior site of radiation are allowed for PD-L1 characterization, other exceptions may be considered after Sponsor consultation). ;4. Have a PD-L1 positive tumor as determined by IHC at a central laboratory from either an archived formalin fixed paraffin embedded (FFPE) tumor sample or a newly obtained biopsy.;5. Have measurable disease based on RECIST 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. ;6. Have a performance status of 0 or 1 on the ECOG Performance Scale.;7. Demonstrate adequate organ function as defined in the protocol.

1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.;2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.;Note: Systemic steroid therapy allowed for subjects in the GBM cohort as long as <= dexamethasone 4 mg, or its steroid equivalent (other exceptions may be considered after sponsor consultation).;3. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., <= Grade 1 or at baseline) from adverse events due to mAbs administered more than 4 weeks earlier. ;4. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., <= Grade 1 or at baseline) from adverse events due to a previously administered agent.;Note: Subjects with <= Grade 2 neuropathy or <= Grade 2 alopecia are an exception to this criterion and may qualify for the study.;Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. ;5. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.;6. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.;7. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjøgren*s syndrome will not be excluded from the study.;8. Has evidence of interstitial lung disease.;9. Has an active infection requiring systemic therapy.;10. Has received prior therapy with an anti-PD-1, anti-PD-L1, and anti-PD-L2 (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).;11. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).;12. Is or has an immediate family member (spouse or children) who is investigational site or sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific patient.