A Phase 1b/2 Safety and Tolerability Study of MEDI6469 in Combination With Therapeutic Immune Agents or Monoclonal Antibodies

A Phase 1b/2, Open-label Study to Evaluate the Safety and Tolerability of MEDI6469 in Combination With Immune Therapeutic Agents or Therapeutic Monoclonal Antibodies in Subjects With Selected Advanced Solid Tumors or Aggressive B-cell Lymphomas

The main purpose of this study is to determine the best dose of MEDI6469 that is safe and tolerable when given as monotherapy and in combination with tremelimumab, MEDI4736 (durvalumab), or rituximab in participants with either advanced solid tumors or diffuse large B-cell lymphoma (DLBCL). Tremelimumab and MEDI4736 (durvalumab) will be tested with MEDI6469 in a set of participants with advanced solid tumors while rituximab will be tested with MEDI6469 in participants with DLBCL. MEDI6469 will be tested as monotherapy in participants with advanced solid tumors.

Inclusion Criteria:

• Adults >/= 18 years old
• Histologically or cytologically confirmed advanced solid tumors that are refractory to standard therapy or for which no standard therapy exists (Monotherapy and in Cohorts A and B)
• At least one lesion measurable by RECIST not previously irradiated (Monotherapy and in Cohorts A and B)
• Histologically confirmed DLBCL(Cohort C)
• Adequate organ and marrow function
• ECOG performance status of 0 or 1
• Willingness to provide consent for biopsy samples

Exclusion Criteria:

• Prior exposure to immunotherapy (either as a single agent or in combination) including but not limited to CD137 or OX40 agonists, anti-CTLA-4, anti-PD-1, or anti-PD-L1, anti-PD-L2 antibody or pathway-targeting agents
• History of organ transplant that requires use of immunosuppressives
• History of primary immunodeficiency or tuberculosis
• Active or prior documented autoimmune disease within the past 3 years
• Active or chronic viral hepatitis or history of any type of hepatitis within the last 6 months
• Major surgical procedure within 30 days prior to the first dose of investigational product or still recovering from prior surgery
• Women who are pregnant or lactating