Pembrolizumab in Treating Patients with Metastatic or Locally Advanced Microsatellite Unstable Solid Tumors

Inclusion Criteria

• Cohort A: patients with histologically proven metastatic or locally advanced MSI colorectal adenocarcinoma
• Cohort B: patients with histologically proven metastatic or locally advanced microsatellite stable (MSS) colorectal adenocarcinoma
• Cohort C: patients with histologically proven metastatic or locally advanced non-colorectal MSI solid tumor malignancies
• Cohort D: Patients with histologically proven metastatic or locally advanced solid tumor malignancies that are microsatellite stable with a documented mutation burden level measured at >= 20 mutations per megabase pairs (MB)
• Patients with the presence of at least one lesion with measurable disease as defined by 10 mm in longest diameter for a soft tissue lesions or 15 mm in short axis for a lymph node by RECIST 1.1 and irRC criteria for response assessment
• Patients must agree to have a biopsy at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator)
• Patients with colon cancer (cohort A and B) must have received at least 2 prior cancer therapy regimens; patients with other cancer types (cohort C) must have received at least 1 prior cancer therapy regimen; patients in cohort D must have received at least 1 prior cancer therapy regimen; patients must have progressive disease on study entry
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy of greater than 3 months
• Absolute neutrophil count >= 1,000/mcL
• Platelets >= 90 x 10^3/uL
• Hemoglobin >= 9.0 g/dL
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (patients with diagnosed Gilbert’s syndrome will not be excluded if their direct bilirubin is within normal institutional limits, 10 x ULN if hepatic metastases)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN (10 x ULN if hepatic metastases)
• Creatinine =< 2 x ULN
• Female patient of childbearing potential has a negative urine or serum pregnancy test; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; the serum pregnancy test must be negative for the patient to be eligible
• Female patients enrolled in the study, who are not free from menses for > 2 years, post hysterectomy/oophorectomy, or surgically sterilized, must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from heterosexual activity throughout the study, starting with visit 1 through 120 days after the last dose of study therapy; approved contraceptive methods include for example; intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, female condoms with spermicide, or oral contraceptives; spermicides alone are not an acceptable method of contraception
• Male patients must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study therapy
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• 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 1 week prior to trial treatment; this is not applicable to patients with primary brain tumors
• Patient who has had chemotherapy, or biological cancer therapy within 2 weeks prior to the first dose of study drug; patient who has had radiation within 2 weeks prior to the first dose of study drug
• Patient is currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study drug
• Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study
• Patients who have had surgery within 4 weeks of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc), celiac plexus block, and biliary stent placement
• Patients with a history of prior treatment with anti-programmed cell death (PD-1), anti-PD-L1, anti-programmed cell death 1 ligand 2 (PD-L2), anti-tumor necrosis factor receptor superfamily, member 9 (CD137), anti-tumor necrosis factor receptor superfamily, member 4 (OX-40), anti- TNF receptor superfamily member 5 (CD40), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies
• Patients who have received any of the following concomitant therapy: interleukin (IL)-2, interferon or other non-study immunotherapy regimens; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses) within 1 week prior to first dose; Note: systemic steroid therapy allowed for subjects with primary brain tumors as long as =< dexamethasone 4 mg or its steroid equivalent
• Patients who have received a live vaccine within 4 weeks prior to or after any dose of MK-3475 * Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
• Patients receiving growth factors including, but not limited to, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug administration; use of such agents while on study is also prohibited; prior use of growth factors should be documented in the patient’s medical history
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Has an 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 (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic 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
• Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft; instances where loss of the graft is not a clinical concern (such as dental bone grafts or skin grafts placed only to promote skin growth) can be approved by the protocol chair; patients with a history of allogeneic hematopoietic stem cell transplant will be excluded
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Patients with a known active hepatitis B (e.g., hepatitis B surface antigen[HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• Patients with evidence of interstitial lung disease
• Patients with a pulse oximetry of < 92% on room air
• Patients on supplemental home oxygen
• Patient is, at the time of signing informed consent, a regular user (including “recreational use”) of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
• Women who are pregnant or breastfeeding
• Women with a positive pregnancy test on enrollment or prior to investigational product administration
• Sexually active fertile men not using effective birth control if their partners are women of childbearing potential (WOCBP)