Phase 2 Study of Plamotamab Combined With Tafasitamab Plus Lenalidomide Versus Tafasitamab Plus Lenalidomide in Relapsed or Refractory (R/R) Diffuse Large-cell B-cell Lymphoma (DLBCL)

April 4, 2024 updated by: Xencor, Inc.

A Phase 2 Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of XmAb13676 (Plamotamab) Combined With Tafasitamab Plus Lenalidomide Versus Tafasitamab Plus Lenalidomide in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

The purpose of this study is to investigate the safety and effectiveness of plamotamab when it is given with tafasitamab and lenalidomide in participants with relapsed or refractory DLBCL.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is a randomized, multicenter, open-label, Phase 2 study of plamotamab combined with tafasitamab plus lenalidomide versus tafasitamab plus lenalidomide in adult participants with DLBCL who have relapsed after or are refractory to at least 1 prior line of therapy, which must have included multi-agent chemoimmunotherapy inclusive of an anti-cluster of differentiation (CD) 20 monoclonal antibody, and who are not candidates for autologous stem-cell transplantation (ASCT), refuse ASCT, or relapse after ASCT.

The study was planned to be performed sequentially, with Part 1A (Safety run-in, with a lower plamotamab dose), Part 1B (Safety run-in, with the target plamotamab dose) and Part 2 (Open-Label, randomized). The study was terminated by the Sponsor during Part 1A of the study. No participants were enrolled in Part 1B or Part 2.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Rennes Cedex, France
        • CHU de Rennes - Hôpital de Pontchaillou
  • Spain
      • Granada, Spain
        • Hospital Universitario Virgen de las Nieves
  • United States
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed diagnosis of DLBCL, not otherwise specified, including DLBCL arising from low grade lymphoma
  • CD20+ and CD19+ lymphoma
  • Archival paraffin embedded tumor tissue or unstained slides must be available for retrospective cell of origin determination
  • Relapsed or refractory
  • At least 1 prior systemic line(s) of therapy, one of which must have included multi-agent chemoimmunotherapy that includes an anti-CD20 monoclonal antibody.
  • At least 1 bidimensionally measurable disease site. The lesion must have a greatest transverse diameter of ≥ 1.5 centimeter (cm) and greatest perpendicular diameter of ≥ 1.0 cm at baseline. The lesion must have a positive finding on positron emission tomography (PET) scan
  • Ineligible for or refuse hematopoietic stem cell transplantation (HSCT).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Completed vaccination for the SARS-CoV-2 virus prior to study entry
  • Fertile participants must agree to use 2 highly effective methods of birth control during for at least 6 months (male participants) and 8 months (female participants) after the last dose of study treatment

Exclusion Criteria:

  • Any other histological type of lymphoma, including high-grade B-cell lymphoma, including those with myelocytomatosis oncogene (MYC) and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements primary mediastinal (thymic) large B cell (PMBL) or Burkitt lymphoma
  • A prior diagnosis of chronic lymphocytic leukemia (CLL) (Richter's Transformation)
  • Primary central nervous system lymphoma

Exclusionary Previous and Current Treatment:

  • Previously received treatment with an anti-CD20 × anti-CD3 bispecific antibody (bsAb)
  • Anti-CD20 therapy (for example, rituximab) within 21 days prior to study entry

  • Participants who have, within 14 days prior study entry:

    • Chemotherapy, radiotherapy, or other lymphoma-specific therapy not including anti CD20 therapy
    • Small molecule or investigational anticancer agents within 6 elimination half-lives
    • Received live vaccines within 30 days
    • Required systemic anti-infective therapy for active, intercurrent infections

  • Participants who have had the following prior therapies or treatments:

    • Were previously treated with CD19-targeted therapy, including chimeric antigen receptor-T cell (CAR-T), unless current biopsy is CD19+
    • Have a history of hypersensitivity to compounds of similar biological or chemical composition to tafasitamab, immunomodulatory imide drugs (IMiDs)
    • Previous allogenic stem cell transplantation
    • Have a history of deep venous thrombosis/embolism, threatening thromboembolism
    • Concurrently use other anticancer or experimental treatments

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1A: Plamotamab (lower dose), Tafasitamab, and Lenalidomide
Drug: Plamotamab will be administered at a lower dose in addition to tafasitamab (12 milligrams [mg]/kilograms [kg] intravenously) plus lenalidomide (25 mg orally). This cohort was planned to enroll sequentially prior to Part 1B.
Biological: Plamotamab
Biological
Other Names:
  • XmAb13676
Biological: Tafasitamab
Biological
Drug: Lenalidomide
Drug
Experimental: Part 1B: Plamotamab (target dose), Tafasitamab, and Lenalidomide
Drug: Plamotamab will be administered at the target dose in addition to tafasitamab (12 mg/kg intravenously) plus lenalidomide (25 mg orally). This cohort was planned to enroll sequentially after Part 1A.
Biological: Plamotamab
Biological
Other Names:
  • XmAb13676
Biological: Tafasitamab
Biological
Drug: Lenalidomide
Drug
Experimental: Part 2A :Plamotamab, Tafasitamab, and Lenalidomide
Drug: Plamotamab will be administered at protocol defined dose in addition to tafasitamab (12 mg/kg intravenously) plus lenalidomide 25 mg (orally).
Biological: Plamotamab
Biological
Other Names:
  • XmAb13676
Biological: Tafasitamab
Biological
Drug: Lenalidomide
Drug
Active Comparator: Part 2B: Tafasitamab and Lenalidomide
Drug: Tafasitamab (12 mg/kg intravenously) plus lenalidomide 25 mg (orally).
Biological: Tafasitamab
Biological
Drug: Lenalidomide
Drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1 A: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time Frame: From first dose of study drug up to end of treatment (maximum treatment exposure: 303 days)
An adverse event (AE) was any untoward medical occurrence in a study participant. The AE did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug. AEs may have included the onset of new illness and the exacerbation of preexisting conditions. TEAEs were defined as events with onset dates on or after the start of study treatment or events that were present before the first infusion of study treatment and subsequently worsened in severity. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
From first dose of study drug up to end of treatment (maximum treatment exposure: 303 days)
Part 1 A: Number of Participants With Cytokine Release Syndrome
Time Frame: From first dose of study drug up to end of treatment (maximum treatment exposure: 303 days)
Cytokine release syndrome was defined as "a supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells". A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
From first dose of study drug up to end of treatment (maximum treatment exposure: 303 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xencor, Inc.

Investigators

  • Study Director: Michael Chiarella, Senior Director, Clinical Science, Clinical Development

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 15, 2022

Primary Completion (Actual)

February 21, 2023

Study Completion (Actual)

February 21, 2023

Study Registration Dates

First Submitted

April 4, 2022

First Submitted That Met QC Criteria

April 11, 2022

First Posted (Actual)

April 14, 2022

Study Record Updates

Last Update Posted (Actual)

April 30, 2024

Last Update Submitted That Met QC Criteria

April 4, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XmAb13676-03

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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