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)

NCT ID: NCT05328102

Last Updated: 2024-04-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-15
• Study Completion Date: 2023-02-21

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.

Conditions

Diffuse Large-cell B-cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Plamotamab

Intervention Type: BIOLOGICAL

Biological

Tafasitamab

Intervention Type: BIOLOGICAL

Biological

Lenalidomide

Intervention Type: DRUG

Drug

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.

Group Type: EXPERIMENTAL

Plamotamab

Intervention Type: BIOLOGICAL

Biological

Tafasitamab

Intervention Type: BIOLOGICAL

Biological

Lenalidomide

Intervention Type: DRUG

Drug

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).

Group Type: EXPERIMENTAL

Plamotamab

Intervention Type: BIOLOGICAL

Biological

Tafasitamab

Intervention Type: BIOLOGICAL

Biological

Lenalidomide

Intervention Type: DRUG

Drug

Part 2B: Tafasitamab and Lenalidomide

Drug: Tafasitamab (12 mg/kg intravenously) plus lenalidomide 25 mg (orally).

Group Type: ACTIVE_COMPARATOR

Tafasitamab

Intervention Type: BIOLOGICAL

Biological

Lenalidomide

Intervention Type: DRUG

Drug

Interventions

Plamotamab

Biological

Intervention Type: BIOLOGICAL

Tafasitamab

Biological

Intervention Type: BIOLOGICAL

Lenalidomide

Drug

Intervention Type: DRUG

Other Intervention Names

XmAb13676

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xencor, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Chiarella

Role: STUDY_DIRECTOR

Senior Director, Clinical Science, Clinical Development

Locations

Swedish Cancer Center

Seattle, Washington, United States

CHU de Rennes - Hopital de Pontchaillou

Rennes, , France

Hospital Universitario Virgen de las Nieves

Granada, , Spain

Countries

United States; France; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

XmAb13676-03

Identifier Type: -

Identifier Source: org_study_id