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

NCT03340766 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 201502902016-002191-27PN348
• Study Type: interventional
• Target: 31
• Locations: 6 countries
• Sites: 22

Brief Summary

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.

Conditions

Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  Dose-limiting toxicities were grade 3-5 adverse events that occurred during the DLT-evaluation period that were judged by the Investigator to be possibly, probably or definitely related to study drug administration. All toxicities were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0: * Grade 3: Severe or medically significant but not immediately life-threatening. * Grade 4: Life-threatening. * Grade 5: Death.

  The DLT evaluation period was 42 days from initiation of pembrolizumab treatment (Day 15 for Cohort Ia and Day 19 for Cohorts IIa and IIIa)

Secondary Outcomes (18)

• Objective Response Rate During the First 12 Weeks Using Revised Response Cheson Criteria

  First 12 weeks of blinatumomab treatment

• Cohort IIIa Only: Objective Response Rate During the First 12 Weeks Using the Lugano Classification

  First 12 weeks of blinatumomab treatment

• Objective Response Rate During the Treatment Period Using Revised Response Cheson Criteria

  From Day 1 to 30 days after last dose of either blinatumomab or pembrolizumab administration; the overall median duration of treatment was 87 days.

• Cohort IIIa Only: Objective Response Rate During the Treatment Period Using the Lugano Classification

  From study Day 1 to 30 days after last dose of either blinatumomab or pembrolizumab administration; the overall median duration of treatment was 87 days.

• Complete Response Rate During the First 12 Weeks Using the Revised Response Cheson Criteria

  First 12 weeks of blinatumomab treatment

Study Arms (4)

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

EXPERIMENTAL

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.

Drug: Blinatumomab; Drug: Pembrolizumab

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

EXPERIMENTAL

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.

Drug: Blinatumomab; Drug: Pembrolizumab

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

EXPERIMENTAL

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.

Drug: Blinatumomab; Drug: Pembrolizumab

Expansion Cohort

EXPERIMENTAL

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

Drug: Blinatumomab; Drug: Pembrolizumab

Interventions

Blinatumomab DRUG

Up to 2 cycles of blinatumomab may be given, where cycle 1 lasts 8 weeks, and cycle 2 lasts 28 days. The treatment is given as a continuous intravenous infusion.

Also known as: Blincyto, AMG 103, Formerly known as MT103 or bscCD19xCD3

Cohort IIIa: Blinatumomab 9/28/112 µg/day + Pembrolizumab; Cohort IIa: Blinatumomab 9/28/56 µg/day + Pembrolizumab; Cohort Ia: Blinatumomab 9/28 µg/day + Pembrolizumab; Expansion Cohort

Pembrolizumab DRUG

One cycle of pembrolizumab is a 200 mg IV injection lasting 30 minutes. One cycle will be given every 3 weeks until disease progression, or for a maximum of 35 cycles.

Also known as: Keytruda, MK-3475

Cohort IIIa: Blinatumomab 9/28/112 µg/day + Pembrolizumab; Cohort IIa: Blinatumomab 9/28/56 µg/day + Pembrolizumab; Cohort Ia: Blinatumomab 9/28 µg/day + Pembrolizumab; Expansion Cohort

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (22)

Research Site

La Jolla, California, 92093-0960, United States

Location

Research Site

Charleston, South Carolina, 29424, United States

Location

Research Site

Greenville, South Carolina, 29607, United States

Location

Research Site

Darlinghurst, New South Wales, 2010, Australia

Location

Research Site

St Leonards, New South Wales, 2065, Australia

Location

Research Site

Adelaide, South Australia, 5000, Australia

Location

Research Site

East Melbourne, Victoria, 3002, Australia

Location

Research Site

Geelong, Victoria, 3220, Australia

Location

Research Site

Melbourne, Victoria, 3004, Australia

Location

Research Site

Murdoch, Western Australia, 6150, Australia

Location

Research Site

Créteil, 94010, France

Location

Research Site

Nantes, 44035, France

Location

Research Site

Pierre-Bénite, 69495, France

Location

Research Site

Heidelberg, 69120, Germany

Location

Research Site

Ulm, 89081, Germany

Location

Research Site

Würzburg, 97080, Germany

Location

Research Site

Maastricht, 6229 HX, Netherlands

Location

Research Site

Rotterdam, 3015 CN, Netherlands

Location

Research Site

Santander, Cantabria, 39008, Spain

Location

Research Site

Salamanca, Castille and León, 37007, Spain

Location

Research Site

Barcelona, Catalonia, 08025, Spain

Location

Research Site

Madrid, 28046, Spain

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Recurrence; Lymphoma, Large B-Cell, Diffuse

Interventions

blinatumomab; N,N-dicyclohexyl-isoborneol-10-sulfonamide; pembrolizumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

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

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 23, 2017
• First Posted: November 14, 2017
• Study Start: March 16, 2018
• Primary Completion: November 6, 2020
• Study Completion: August 14, 2023
• Last Updated: October 17, 2024
• Results First Posted: February 25, 2022

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

DE (3); ES (4); FR (3); US (3); AU (7); NL (2)