Study of Pembrolizumab Plus Chemotherapy in Patients With Advanced Cancer (PembroPlus)

Inclusion Criteria:

1. Patient at least 18 years old and has definitive histologically or cytologicallyconfirmed metastatic solid tumor 2. Patient has one or more metastatic tumors measurable byCT scan (or PET/CT, if patient is allergic to CT contrast media) 3. The investigator willselect the appropriate treatment arm for the patient with the following requirements: (a)Patients cannot have had prior progression or intolerance on the single agent chemotherapyand then enrolled on an arm with that same single agent chemotherapy plus pembro (b) Thechemotherapy on the arm selected must be considered standard of care or listed in the NCCNguidelines (www.nccn.org) for that cancer type 4. Have recovered from acute toxicities ofprior treatment:

2. > 3 weeks must have elapsed since receiving any investigational agent

3. > 2 weeks must have elapsed since receiving any radiotherapy, or ≥ 3 weeks or 5half-lives whichever is shorter for treatment with cytotoxic or biologic agents (≥ 6weeks for mitomycin or nitrosoureas). Chronic treatment with non-investigationalgonadotropin-releasing hormone analogs or other hormonal or supportive care ispermitted 5. Patient has adequate biological parameters as demonstrated by thefollowing blood counts at time of screening: 6. Absolute neutrophil count (ANC) > 1500mm3, platelet count ≥ 100×109 L, hemoglobin ≥ 9 g/dL 7. Serum creatinine ≤2.0, totalbilirubin ≤ 2 mg/dL, AST/ALT ≤ 5 times the upper limit of normal (ULN) range (except:for the nab-paclitaxel containing arm, bilirubin ≤ 1.25 times the ULN and for thedocetaxel containing arm, bilirubin must be within institutional normal limits andAST/ALT ≤ 1.5 times the ULN) 8. Thyroid stimulating hormone (TSH) within institutionalnormal limits. If TSH is above the upper limit of normal range, then a free T4 withininstitutional normal limits is acceptable 9. Persistent prior systemic therapynon-hematologic AE grade ≥ 2 (except alopecia or correctable electrolyte abnormalitywith supplementation) 10. Patient has a Karnofsky performance status (KPS) ≥ 70 11.Women of child-bearing potential (i.e., women who are pre-menopausal or not surgicallysterile) must be willing to use an acceptable contraceptive method (abstinence, oralcontraceptive or double barrier method) for the duration of the study and for 4 monthsfollowing the last dose of pembrolizumab and 30 days following the last dose ofchemotherapy on this trial, and must have a negative urine or serum pregnancy testwithin 2 weeks prior to beginning treatment on this trial Phase II only

4. Patients must have metastatic sarcoma to be enrolled in the following 4 arms:pembro plus gemcitabine, pembro plus gemcitabine and docetaxel, pembro plusgemcitabine and vinorelbine, and pembro plus liposomal doxorubicin

5. Patients must have metastatic pancreatic adenocarcinoma to be enrolled in thepembro plus gemcitabine and nab-paclitaxel arm

6. Patients must have extensive-stage small cell lung cancer to be enrolled in thepembro plus irinotecan arm

Exclusion Criteria:

1. Active clinically serious infection > CTCAE (version 4.03) Grade 2.

2. Serious non-healing wound, ulcer, or bone fracture

3. Patient has known brain metastases, unless previously treated and well-controlled forat least 1 month (defined as clinically stable, no edema, no steroids and stable in 2scans at least 4 weeks apart)

4. Inability to complete informed consent process and adhere to the protocol treatmentplan and follow-up requirements

5. Patient has known active infection with HIV, hepatitis B, or hepatitis C (patients areNOT required to be tested for the presence of such viruses prior to therapy on thisprotocol)

6. Requiring daily corticosteroid dose ≥ 10 mg prednisone or equivalent per day

7. Patient has undergone major surgery, other than diagnostic surgery (e.g., surgery doneto obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior toDay 1 of treatment in this study

8. Patient has a history of allergy or hypersensitivity to any of the study drugs or anyof their excipients, or the patient exhibits any of the events outlined in theContraindication or Special Warnings and Precautions sections of the product orcomparator SmPC or Prescribing Information

9. Patient has serious medical risk factors involving any of the major organ systems, orserious psychiatric disorders, which could compromise the patient's safety or thestudy data integrity

10. Patient will be receiving any other anti-cancer therapy during participation in thistrial

11. Prior treatment with pembro. Receipt of other PD-1 inhibitors or PD-L1 inhibitors isallowed

12. Active or prior documented autoimmune disease requiring systemic treatment within thepast 2 years Phase II portion only

13. Patients with a history of more than one primary cancer, with the exception of:

14. curatively resected nonmelanomatous skin cancer;

15. curatively treated cervical carcinoma in-situ; or

16. other primary solid tumor treated with curative intent and no known active diseasepresent and no treatment administered during the 2 years prior to enrollment