Phase 2 Study of Plamotamab Combined With Tafasitamab Plus Lenalidomide Versus Tafasitamab Plus Lenalidomide in R/R DLBCL

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

Detailed Description
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This is a randomized, multicenter, open-label, Phase 2 study of plamotamab combined with tafasitamab plus lenalidomide versus tafasitamab plus lenalidomide in adult subjects 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-CD20 monoclonal antibody, and who are not candidates for ASCT, refuse ASCT, or relapse after ASCT. The study will enroll and evaluate subjects in a single arm for safety and determination of dose and dose schedule.

Official Title
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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

Conditions
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Diffuse Large-cell B-cell Lymphoma

Intervention / Treatment
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* Biological: plamotamab
* Biological: tafasitamab
* Drug: lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of DLBCL, NOS, 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 cm and greatest perpendicular diameter of ≥ 1.0 cm at baseline. The lesion must have a positive finding on PET scan Ineligible for or refuse hematopoietic stem cell transplantation (HSCT). ECOG) performance status of 0 to 2 Completed vaccination for the SARS-CoV-2 virus prior to study entry Fertile subjects must agree to use 2 highly effective methods of birth control during for at least 6 months (male subjects) and 8 months (female subjects) after the last dose of study treatment Exclusion Criteria: Any other histological type of lymphoma, including high-grade B-cell lymphoma, including those with MYC and BCL2 and/or BCL6 rearrangements primary mediastinal (thymic) large B cell (PMBL) or Burkitt lymphoma A prior diagnosis of CLL (Richter's Transformation) Primary central nervous system (CNS) lymphoma Exclusionary Previous and Current Treatment: Previously received treatment with an anti-CD20 × anti-CD3 bsAb Anti-CD20 therapy (eg, rituximab) within 21 days prior to study entry Subjects 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 (see Section 7.2 for details) within 30 days Required systemic anti-infective therapy for active, intercurrent infections Subjects who have had the following prior therapies or treatments: Were previously treated with CD19-targeted therapy, including CAR-T, unless current biopsy is CD19+ Have a history of hypersensitivity to compounds of similar biological or chemical composition to tafasitamab, IMiDs Previous allogenic stem cell transplantation Have a history of deep venous thrombosis/embolism, threatening thromboembolis Concurrently use other anticancer or experimental treatments

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Part 1 Single Arm Multiple Dose Followed by Part 2 Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>Drug: plamotamab administered at protocol defined dose in addition to tafasitamab (12 mg/kg intravenously) plus lenalidomide (25mg p.o.) | Biological: plamotamab<br>* Biological<br>Biological: tafasitamab<br>* Biological<br>Drug: lenalidomide<br>* Drug<br>|
| Experimental: Part 2<br>Drug: plamotamab administered at protocol defined dose in addition to tafasitamab (12 mg/kg intravenously) plus lenalidomide 25mg (p.o.) | Biological: plamotamab<br>* Biological<br>Biological: tafasitamab<br>* Biological<br>Drug: lenalidomide<br>* Drug<br>|
| Active Comparator: Part 2B<br>Drug: tafasitamab (12 mg/kg intravenously) plus lenalidomide 25mg (p.o.) | Biological: tafasitamab<br>* Biological<br>Drug: lenalidomide<br>* Drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| For Part 1: safety as measured by incidence of Treatment Emergent Adverse Events (TEAEs), including Cytokine Release Syndrome (CRS) |  | 4 months | 
| For Part 2: Progression-free Survival (PFS) |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBCL, NOS, Diffuse Large B-cell Lymphoma, Transformed indolent Lymphoma