A Phase 1b/2, Open-Label Study To Evaluate The Safety And Tolerability Of Medi6469 In Combination With Immune Therapeutic Agents Or Therapeutic Mabs In Patients With Selected Advanced Solid Tumors Or Aggressive B-Cell Lymphomas.

TPS3091 Background: Anti-CTLA-4 and anti-PD-1/PD-L1 have shown antitumor activity in 10–30% of patients (pts) with select tumors. Combinations of co-stimulatory agonists, such as OX40, and antagonist Abs against the T-cell checkpoints CTLA-4 or PD-L1 could synergize to yield higher response rates. Additionally, nonclinical models show OX40 cell surface expression is induced following activation of NK cells. OX40 ligation promotes enhanced NK cell activity, suggesting greater antitumor activity could be achieved with an OX40 agonist in combination with an anti-CD20 antibody engaging NK cells for antitumor activity. Depleting B cells with rituximab could decrease immunogenicity of murine MEDI6469 by decreasing anti-drug Ab production. MEDI6469, an agonist human OX40 receptor murine mAb, showed clinical activity in a Phase 1 study and is being evaluated as monotherapy and in combination with tremelimumab (anti-CTLA-4) or MEDI4736 (anti-PD-L1) in pts with select advanced solid tumors, or with rituximab (anti-...