Diffuse Large-cell B-cell Lymphoma
Conditions
Keywords
DLBCL, NOS, Diffuse Large B-cell Lymphoma, Transformed indolent Lymphoma
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.
Interventions
Sponsors
Xencor, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part 1 Single Arm Multiple Dose Followed by Part 2 Randomized
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 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. |
| Part 1 A: Number of Participants With Cytokine Release Syndrome | 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. |
Countries
France, Spain, United States
Participant flow
Recruitment details
The study planned to enroll participants at 11 sites (1 in the United States, 7 in France, 2 in Spain, and 1 in South Korea). However, due to early study termination only 3 participants were enrolled and dosed at a single site in the United States.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Part 1A: Plamotamab (Lower Dose), Tafasitamab, and Lenalidomide Plamotamab was administered at a lower dose in addition to tafasitamab (12 mg/kg intravenously) plus lenalidomide (25 mg orally). | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Part 1A: Plamotamab (Lower Dose), Tafasitamab, and Lenalidomide |
|---|---|
| Age, Customized >=18 years | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 3 / 3 |
Outcome results
Primary
Part 1 A: Number of Participants With Cytokine Release Syndrome
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.
Time frame: From first dose of study drug up to end of treatment (maximum treatment exposure: 303 days)
Population: Enrolled Analysis Set: All participants who signed the informed consent form, were determined to be eligible, and received Day -8 tafasitamab dose (Study Day 1). The study was terminated by the Sponsor during Part 1A of the study. No participants were enrolled in Part 1B or Part 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1A: Plamotamab (Lower Dose), Tafasitamab, and Lenalidomide | Part 1 A: Number of Participants With Cytokine Release Syndrome | 2 Participants |
Primary
Part 1 A: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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.
Time frame: From first dose of study drug up to end of treatment (maximum treatment exposure: 303 days)
Population: Enrolled Analysis Set: All participants who signed the informed consent form, were determined to be eligible, and received Day -8 tafasitamab dose (Study Day 1). The study was terminated by the Sponsor during Part 1A of the study. No participants were enrolled in Part 1B or Part 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1A: Plamotamab (Lower Dose), Tafasitamab, and Lenalidomide | Part 1 A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 Participants |