A Study in Advanced Cancers Using Ramucirumab (LY3009806) and Other Targeted Agents

Inclusion Criteria:

* Study Arm 1:

  * histopathologically confirmed advanced or metastatic colorectal cancer, excluding primary tumors of appendiceal origin
  * have at least 1 measurable lesion assessable by radiological imaging. Tumor lesions located in a previously irradiated area are considered measureable if progression has been demonstrated in such lesions
  * have received prior second-line treatment with oxaliplatin and/or irinotecan, and no other licensed/standard-of-care therapies are available. If the participant has RAS wild type colorectal cancer, he or she also must have received prior treatment with an epidermal growth factor receptor monoclonal antibody
* Study Arm 2

  * pathologically confirmed mantle cell lymphoma (MCL), with (a) measurable nodal disease on positron emission tomography computed tomography (PET-CT) per Lugano classification. Prior to enrollment, pathology must be reviewed and confirmed at the investigational site where the participant is entered
  * have MCL that relapsed after or is refractory to (a) first-line combination chemotherapy with or without stem cell transplant and (b) at least 1 other locally available therapy
  * provide a newly obtained tumor tissue sample. Tumor tissue biopsies may be taken by surgical resection, core needle biopsy, or fine needle biopsy
* All Study Arms:

  * have not received previous systemic therapy (including investigational agents) targeting programmed cell death protein 1 (PD-1)/ PD-1 ligand (PDL 1) or PD-1/PDL-2 signaling pathways. Prior therapy with other immune checkpoint inhibitors, including but not limited to, anti-CD137 antibody or anticytotoxic T-lymphocyte-associated antigen-4 antibody, is not permitted
  * have adequate organ function
  * are, in the judgment of the investigator, appropriate candidates for experimental therapy after available standard therapies have failed to provide clinical benefit
  * have discontinued all previous treatments for cancer and recovered from the acute effects of therapy, other than less than or equal to Grade 2 neuropathy or nonserious and nonlife-threatening toxicities such as alopecia, altered taste, and nail changes
  * have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale
  * men and women must agree to the use an effective method of contraception during the study and for at least 3 months post last dose of study drug administration. Women of child-bearing potential must have negative serum and urine pregnancy tests at screening and during each treatment cycle, respectively

Exclusion Criteria:

* Study Arm 1

  * have a serious illness or medical condition including, but not limited to, the following: active or uncontrolled clinically serious infection; inadequate biliary drainage with evidence of unresolved biliary obstruction
* Study Arm 2

  * have a serious illness or medical condition including, but not limited to, the following: active or uncontrolled clinically serious infection, including chronic viral hepatitis
* All Arms:

  * have prior or concurrent malignancies, inclusive of hematologic, primary brain tumor, sarcoma, and other solid tumors, unless in complete remission with no therapy for a minimum of 5 years
  * have active gastrointestinal (GI) disease characterized by inflammatory bowel disease, malabsorption syndrome, or frequent Grade 2 or more diarrhea
  * are pregnant or breastfeeding
  * have previously documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression
  * have experienced any of the following: a major surgical procedure, significant traumatic injury, non-healing wound, peptic ulcer, or bone fracture less than or equal to 28 days prior to enrollment, or placement of a subcutaneous venous access device less than or equal to 7 days prior to the first dose of study treatment unless the procedure is of low risk of bleeding in the judgment of the investigator
  * have an elective or a planned major surgery during the course of the trial
  * have a known allergy or hypersensitivity reaction to any of the treatment components
  * have uncontrolled hypertension
  * have experienced any arterial thromboembolic event within 6 months prior to enrollment
  * have experienced any Grade 3 or 4 venous thromboembolic event that is considered by the investigator to be life threatening or that is symptomatic and not adequately treated by anticoagulation therapy, within 6 months prior to enrollment
  * have a history of GI perforation and/or fistulae within 6 months prior to enrollment
  * have experienced any bleeding episode considered life-threatening, or any Grade 3 or 4 GI/variceal bleeding episode in the 3 months prior to enrollment requiring transfusion or endoscopic or operative intervention
  * have congestive heart failure or poorly controlled cardiac arrhythmia per New York Heart Association Class II-IV heart disease