Clinical Trials /

Open Label Study Investigating the Safety and Efficacy of Blinatumomab in Combination With Pembrolizumab (KEYNOTE-348)

NCT03340766

Description:

Phase 1b: To determine the maximum tolerated dose (MTD) of blinatumomab in combination with pembrolizumab in adult subjects with relapsed or refractory (r/r) DLBCL

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Open Label Study Investigating the Safety and Efficacy of Blinatumomab in Combination With Pembrolizumab (KEYNOTE-348)
  • Official Title: 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) (KEYNOTE-348)

Clinical Trial IDs

  • ORG STUDY ID: 20150290
  • SECONDARY ID: 2016-002191-27
  • NCT ID: NCT03340766

Conditions

  • Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)

Interventions

DrugSynonymsArms
BlinatumomabBlincyto, AMG 103, Formerly known as MT103 or bscCD19xCD3COHORT IIIa
PembrolizumabKeytrudaCOHORT IIIa

Purpose

Phase 1b: To determine the maximum tolerated dose (MTD) of blinatumomab in combination with pembrolizumab in adult subjects with relapsed or refractory (r/r) DLBCL

Trial Arms

NameTypeDescriptionInterventions
COHORT IaExperimentalBlinatumomab 9 to 28 microgram plus Pembrolizumab (day 15).
  • Blinatumomab
  • Pembrolizumab
COHORT IIaExperimentalBlinatumomab 9 to 28 to 56 microgram plus Pembrolizumab (day 19).
  • Blinatumomab
  • Pembrolizumab
COHORT IIIaExperimentalBlinatumomab 9 to 28 to 112 microgram plus Pembrolizumab (day 19).
  • Blinatumomab
  • Pembrolizumab
Expansion CohortExperimentalThis cohort will test the Maximum Tolerated Dose of Blinatumomab in combination with Pembrolizumab identified using cohort design from cohorts Ia, IIa, and IIIa tested in Part 1 of the study.
  • Blinatumomab
  • Pembrolizumab

Eligibility 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 HSCT with adequate organ function after
             proximity to transplantation time exclusions as specified in Exclusion Criteria 208
             and 209

          -  Have measureable disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

          -  Life expectancy of ≥ 12 weeks in the opinion of the Investigator

          -  Subject must be able to provide an evaluable core or incisional/excisional biopsy
             prior to the start of treatment.

        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.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLTs)
Time Frame:Up to study day 63, depending on cohort dosing and schedule
Safety Issue:
Description:Incidence of dose limiting toxicities (DLTs) will be assessed during each cohort

Secondary Outcome Measures

Measure:Objective Response
Time Frame:Study week 10 and every 12 weeks thereafter, for up to 24 months
Safety Issue:
Description:Objective response by Cheson Criteria (2007)
Measure:Progression Free Survival
Time Frame:Study week 10 and every 12 weeks thereafter, for up to 24 months
Safety Issue:
Description:Progression Free Survival (PFS) by Cheson Criteria
Measure:Overall Survival
Time Frame:Subjects followed for survival up to 48 months (24 months after last dose of pembrolizumab)
Safety Issue:
Description:Overall Survival (OS) will be determined for 24 months following the last dose of pembrolizumab.
Measure:Complete Remission
Time Frame:Study week 10 and every 12 weeks thereafter, for up to 24 months
Safety Issue:
Description:Complete Remission (CR) rate by Cheson Criteria
Measure:Duration of response
Time Frame:Study week 10 and every 12 weeks thereafter, for up to 24 months
Safety Issue:
Description:The duration of response (DOR) will be determined using Objective response (OR), Complete remission (CR) and Partial Remission (PR) using Cheson Criteria. The duration will be calculated from the date a response, CR or PR, is first achieved until the earliest date of a disease assessment indicating a relapse event or death, whichever occurs first. Subjects who do not have a relapse event will be censored on their last disease assessment date.
Measure:Blinatumomab Steady state concentration
Time Frame:Up to study day 43, depending on cohort dosing and schedule
Safety Issue:
Description:Pharmacokinetic profile of Blinatumomab: Steady state concentration (Css)
Measure:Blinatumomab Clearance rate
Time Frame:Up to study day 43, depending on cohort dosing and schedule
Safety Issue:
Description:Pharmacokinetic profile of Blinatumomab - Clearance rate
Measure:Pembrolizumab Peak Plasma Concentration
Time Frame:Up to 25 months
Safety Issue:
Description:Pembrolizumab Pharmacokinetic parameter: Peak Plasma Concentration (Cmx)
Measure:Pembrolizumab Minimum plasma concentration
Time Frame:Up to 25 months
Safety Issue:
Description:Pharmacokinetic profile of Pembrolizumab: Minumum plasma concentration (Cmn)
Measure:Pembrolizumab PK Parameter - AUC
Time Frame:Up to 25 months
Safety Issue:
Description:Pharmacokinetic profile of Pembrolizumab: Area under the plasma concentration versus time curve (AUC)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Trial Keywords

  • DLBCL Relapsed post-autologous or allogeneic hematopoietic stem cell transplantation (HSCT)
  • Antibodies
  • Bispecific in combination with PD-1/PD-L1 inhibitor

Last Updated

December 11, 2019