A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects with Advanced Solid Tumors (KEYNOTE 158)

1.Have a histologically or cytologically-documented, advanced (metastatic
and/or unresectable) solid tumor that is incurable and for which prior standard
first-line treatment have failed. Patients must have progressed on or be
intolerant to therapies that are known to provide clinical benefit. There is no
limit to the number of prior treatment regimens.
2.Have one of the following advanced (unresectable and/or metastatic) tumor
types:
(A)Anal Squamous Cell Carcinoma,
(B)Biliary Adenocarcinoma (gallbladder and biliary tree (intrahepatic or
extrahepatic cholangiocarcinoma) except Ampulla of Vater Cancers,
(C)Neuroendocrine Tumors (well- and moderately-differentiated), of the lung,
appendix, small intestine, colon, rectum, or pancreas,
(D)Endometrial Carcinoma (sarcomas and mesenchymal tumors are excluded)
(E)Cervical Squamous Cell Carcinoma,
(F)Vulvar Squamous Cell Carcinoma,
(G)Small Cell Lung Carcinoma,
(H)Mesothelioma (Malignant Pleural Mesothelioma),
(I)Thyroid Carcinoma (Papillary or Follicular Subtype),
(J)Salivary Gland Carcinoma (sarcomas and mesenchymal tumors are excluded)
OR
(K)Any advanced solid tumor (except CRC), which is MSI-H.
(L) Any advanced solid tumor (including CRC*) which is dMMR/MSI-H in patients
from mainland China who are of Chinese descent.
(M) Any advanced solid tumor that has failed at least one line of therapy and
is TMB-H (>=10 mut/Mb, F1CDx assay), excluding dMMR/MSI-H tumors.
3. Have submitted an evaluable tissue sample for biomarker analysis from a
tumor lesion not previously irradiated (exceptions may be considered after
Sponsor consultation). The tumor tissue submitted for analysis must be from a
single tumor tissue specimen and of sufficient quantity and quality to allow
assessment of ALL required primary biomarkers.
Note: SUBJECTS WILL NOT BE ELIGIBLE TO ENROLL INTO GROUPS A-J UNLESS ALL THREE
PRIMARY BIOMARKERS (TUMOR PD-L1 EXPRESSION, GEP SCORE, AND MSI-H STATUS) CAN BE
ASSESSED USING TISSUE FROM THE SAME SINGLE TUMOR SPECIMEN.
4.If enrollment in Groups A-J has moved to biomarker enrichment, have a tumor
that is positive for one or more of the pre-specified primary biomarker(s), as
assessed by the central laboratory. These enrichment biomarkers may be PD-L1
expression by IHC (at a percentage to be prespecified), a positive tumor RNA
GEP score (at a prespecified cut-off), and/or tumor MSI-H.
5.Have radiologically measurable disease based on RECIST 1.1. Independent
central radiologic review must confirm the presence of radiologically
measureable disease based on RECIST 1.1 for the subject to be eligible to
participate in the trial (see Site Imaging Manual for detailed instructions).
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. This
performance status must be confirmed within 3 days prior to the first dose of
pembrolizumab or the subject must be excluded.
7. Life expectancy of at least 3 months.
8. Adequate Organ Function Laboratory Values: Hemoglobin (Hgb) > or = 9.0 g/dL
or > = 5.6 mmol/L, without recent transfusion (defined as a transfusion that
has occurred within 2 weeks of the Hgb measurement)., Refer to protocol for
complete list

- Is currently participating and receiveing study therapy or has been within 4
weeks of the first dose of treatment
-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., -Has an active autoimmune
disease that has required systemic treatment in the 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) or treatment with
drugs (e.g. neomercazol, carbamazole, etc.) that function to decrease the
generation of thyroid hormone by a hyperfunctioning thyroid gland (e.g. in
Graves' disease) is not considered a form of systemic treatment of an
autoimmune disease. , -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., - Has a known additional malignancy within 2
years prior to enrollment with the execption of curatively treated basal cell
carcinoma of the skin, squamous cell carcinoma of the skin, and/or curatively
resected in situ cancers. , - Has known active central nervous system (CNS)
metastases and/or carcinomatous
meningitis., - Has known glioblastoma multiforme of the brainstem., - Has
evidence history of active (non-infectious) pneumonitis that required steroids
or current pneumonitis., Refer to protocol for complete list.