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)

NCT05328102 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: XmAb13676-03
• Study Type: interventional
• Target: 3
• Locations: 3 countries
• Sites: 3

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.

Conditions

Diffuse Large-cell B-cell Lymphoma

Keywords

DLBCL, NOS; Diffuse Large B-cell Lymphoma; Transformed indolent Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  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)

Study Arms (4)

Part 1A: Plamotamab (lower dose), Tafasitamab, and Lenalidomide

EXPERIMENTAL

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: Tafasitamab; Drug: Lenalidomide

Part 1B: Plamotamab (target dose), Tafasitamab, and Lenalidomide

EXPERIMENTAL

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: Tafasitamab; Drug: Lenalidomide

Part 2A :Plamotamab, Tafasitamab, and Lenalidomide

EXPERIMENTAL

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: Tafasitamab; Drug: Lenalidomide

Part 2B: Tafasitamab and Lenalidomide

ACTIVE COMPARATOR

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

Biological: Tafasitamab; Drug: Lenalidomide

Interventions

Plamotamab BIOLOGICAL

Biological

Also known as: XmAb13676

Part 1A: Plamotamab (lower dose), Tafasitamab, and Lenalidomide; Part 1B: Plamotamab (target dose), Tafasitamab, and Lenalidomide; Part 2A :Plamotamab, Tafasitamab, and Lenalidomide

Tafasitamab BIOLOGICAL

Biological

Part 1A: Plamotamab (lower dose), Tafasitamab, and Lenalidomide; Part 1B: Plamotamab (target dose), Tafasitamab, and Lenalidomide; Part 2A :Plamotamab, Tafasitamab, and Lenalidomide; Part 2B: Tafasitamab and Lenalidomide

Lenalidomide DRUG

Drug

Part 1A: Plamotamab (lower dose), Tafasitamab, and Lenalidomide; Part 1B: Plamotamab (target dose), Tafasitamab, and Lenalidomide; Part 2A :Plamotamab, Tafasitamab, and Lenalidomide; Part 2B: Tafasitamab and Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Xencor, Inc.: lead

Study Sites (3)

Swedish Cancer Center

Seattle, Washington, 98104, United States

Location

CHU de Rennes - Hopital de Pontchaillou

Rennes, France

Location

Hospital Universitario Virgen de las Nieves

Granada, Spain

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Pyloric Stenosis, Hypertrophic

Interventions

tafasitamab; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Pyloric Stenosis; Gastric Outlet Obstruction; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Due to the early termination of the study in Part 1A, only 3 participants enrolled. No participants were enrolled in Part 1B or Part 2. Safety data is limited due to the small sample size. No efficacy data was collected for the secondary outcome measures.

Results Point of Contact

• Title: Michael Chiarella
• Organization: Xencor, Inc

mchiarella@xencor.com

858-945-2415

Study Officials

• Michael Chiarella

  Senior Director, Clinical Science, Clinical Development

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 Single Arm Multiple Dose Followed by Part 2 Randomized

Study Record Dates

• First Submitted: April 4, 2022
• First Posted: April 14, 2022
• Study Start: April 15, 2022
• Primary Completion: February 21, 2023
• Study Completion: February 21, 2023
• Last Updated: April 30, 2024
• Results First Posted: April 30, 2024

Record last verified: 2024-04

Locations

US (1); FR (1); ES (1)