Study Investigating the Safety and Efficacy of Blinatumomab in Combination With Pembrolizumab in Adults With Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)

A Phase 1b Open Label Study Investigating the Safety and Efficacy of Blinatumomab in Combination With Pembrolizumab in Adult Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

The primary objective of the study is to determine the maximum tolerated dose (MTD) of blinatumomab in combination with pembrolizumab in adults with relapsed or refractory (r/r) DLBCL.

The study was planned as 2 parts:

• Part 1 will test the safety of up to 3 different blinatumomab target dose levels in combination with pembrolizumab in a rolling 6 design. A Dose Level Review Team (DLRT) will review the safety data to evaluate possible drug effects and dose-limiting toxicities (DLTs).
• Part 2 will consist of an expansion cohort to assess pharmacokinetics (PK), safety, and preliminary efficacy data at the chosen target dose. The part 2 dose will be determined by the totality of the clinical data from part 1 as determined by the DLRT.

Based on the results from Part 1, a decision was made not to proceed with Part 2 of this study.

Secondary objectives of the study are to evaluate the safety, efficacy, and pharmacokinetics (PK) of blinatumomab in combination with pembrolizumab. Tumor response will be evaluated according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al, 2007). With implementation of Protocol Amendment 5, response will also be assessed according to the Lugano Classification (Cheson et al, 2014). Only participants enrolled after implementation of Protocol Amendment 5 (03 December 2019) will have tumor assessments using the Lugano criteria.

Inclusion Criteria:

• Have histologically confirmed diffuse large B-cell lymphoma that is either:
• Refractory after at least one regimen of systemic chemotherapy and/or targeted therapy, or
• In first or later relapse if have received at least 2 systemic regimens since time of diagnosis, or
• Relapsed post-autologous or allogeneic hematopoietic stem cell transplantation (HSCT) with adequate organ function after proximity to transplantation time exclusions
• Have measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Life expectancy of ≥ 12 weeks in the opinion of the Investigator
• Biopsy proven DLBCL (biopsy proven at least at primary diagnosis of DLBCL)

Other Inclusion Criteria May Apply

Exclusion Criteria:

• Richter's transformation (DLBCL arising in the setting of prior chronic lymphocytic leukemia) or primary mediastinal B cell lymphoma (PMBCL)
• History or presence of clinically relevant central nervous system pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
• Has a diagnosis of immunodeficiency or has received systemic steroid therapy (in excess of 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of protocol specified therapy.
• Has undergone prior allogeneic HSCT:
• within the last 5 years OR
• greater than 5 years ago but has active graft versus host disease (GvHD) requiring systemic treatment.
• Has received autologous HSCT within 6 weeks prior to start of treatment.

Other Exclusion Criteria May Apply.