Clinical trial NCT05328102: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Diffuse Large-cell B-cell Lymphoma
Keywords: DLBCL, NOS
Diffuse Large B-cell Lymphoma
Transformed indolent Lymphoma
Lead sponsor: Xencor, Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-14
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Part 1 Single Arm Multiple Dose Followed by Part 2 Randomized
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Part 1 A: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to end of treatment (maximum treatment exposure: 303 days)
measure: Part 1 A: Number of Participants With Cytokine Release Syndrome
timeFrame: From first dose of study drug up to end of treatment (maximum treatment exposure: 303 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Swedish Cancer Center
state: Washington
city: Rennes Cedex
country: France
facility: CHU de Rennes - Hopital de Pontchaillou
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
Study officials:
affiliation: Senior Director, Clinical Science, Clinical Development
name: Michael Chiarella
role: STUDY_DIRECTOR
References: