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

Amgen

Status and phase

Completed

Phase 1

Conditions

Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)

Treatments

Drug: Pembrolizumab

Drug: Blinatumomab

Study type

Interventional

Funder types

Industry

Identifiers

NCT03340766

2016-002191-27 (EudraCT Number)

20150290

PN348 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

31 patients

Sex

All

Ages

18 to 100 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

31 participants in 4 patient groups

Cohort Ia: Blinatumomab 9/28 µg/day + Pembrolizumab

Experimental group

Description:

Participants received blinatumomab administered as a continuous intravenous infusion (CIVI) for 8 weeks followed by a 28-day treatment-free interval. Participants with stable disease or better may have received a second 28-day consolidation cycle. The starting dose of each cycle was 9 µg/day for the first 7 days then 28 µg/day for the remaining days of treatment. Starting on Day 15 participants also received 200 mg pembrolizumab administered by intravenous (IV) infusion every 3 weeks (Q3W) until disease progression or for up to 35 cycles.

Treatment:

Drug: Blinatumomab

Drug: Pembrolizumab

Cohort IIa: Blinatumomab 9/28/56 µg/day + Pembrolizumab

Experimental group

Description:

Participants received blinatumomab administered as a continuous intravenous infusion for 8 weeks followed by a 28-day treatment-free interval. Participants with stable disease or better may have received a second 28-day consolidation cycle. The starting dose of each cycle was 9 µg/day for the first 7 days, 28 µg/day for 7 days then 56 µg/day for the remaining days of treatment. Starting on Day 19 participants also received 200 mg pembrolizumab administered by IV infusion Q3W until disease progression or for up to 35 cycles.

Treatment:

Drug: Blinatumomab

Drug: Pembrolizumab

Cohort IIIa: Blinatumomab 9/28/112 µg/day + Pembrolizumab

Experimental group

Description:

Participants received blinatumomab administered as a continuous intravenous infusion for 8 weeks followed by a 28-day treatment-free interval. Participants with stable disease or better may have received a second 28-day consolidation cycle. The starting dose of each cycle was 9 µg/day for the first 7 days, 28 µg/day for 7 days then 112 µg/day for the remaining days of treatment. Starting on Day 19 participants also received 200 mg pembrolizumab administered by IV infusion Q3W until disease progression or for up to 35 cycles.

Treatment:

Drug: Blinatumomab

Drug: Pembrolizumab

Expansion Cohort

Experimental group

Description:

This cohort will test the maximum tolerated dose of blinatumomab in combination with pembrolizumab identified in Part 1 of the study.

Treatment:

Drug: Blinatumomab

Drug: Pembrolizumab

Trial documents