Loncastuximab Tesirine and Mosunetuzumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma

NCT05672251 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 22414NCI-2022-10312P30CA033572
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the safety and how well of loncastuximab tesirine when given together with mosunetuzumab works in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Loncastuximab tesirine is a monoclonal antibody, loncastuximab, linked to a toxic agent called tesirine. Loncastuximab attaches to anti-CD19 cancer cells in a targeted way and delivers tesirine to kill them. Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving loncastuximab tesirine with mosunetuzumab may help treat patients with relapsed or refractory diffuse large B-cell lymphoma.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Grade 3b Follicular Lymphoma; Recurrent High Grade B-Cell Lymphoma; Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma; Recurrent Transformed Chronic Lymphocytic Leukemia; Recurrent Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Grade 3b Follicular Lymphoma; Refractory High Grade B-Cell Lymphoma; Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma; Refractory Transformed Chronic Lymphocytic Leukemia; Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Unacceptable toxicity (Safety Lead-in)

  Defined as any toxicity occurring during the first cycle of treatment for patients enrolled on DL 1, or during the first two cycles of treatment for patients enrolled on DL -1, within at most one out of six patients treated. Will be conducted per the rolling six design.

  Up to 30 days post-last dose of protocol therapy

• Overall response rate (ORR) (Phase 2)

  Defined as the proportion of response-evaluable participants that achieve a best response of either CR or PR. Will use a Simon's 2-stage Minimax design, occur within at most 26 responders. Will be estimated along with the 95% exact binomial confidence interval.

  Up to 2 years post-last dose

Secondary Outcomes (5)

• Incidence of adverse events

  Up to 30 days post-last dose of protocol therapy

• Complete response rate (CR) rate

  Up to 2 years post-last dose

• Duration of response (DOR)

  Up to 2 years post-last dose

• Progression-free survival (PFS)

  From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier, assessed up to 2 years post-last dose

• Overall Survival (OS)

  From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier, assessed up to 2 years post-last dose

Study Arms (1)

Treatment (oncastuximab tesirine, mosunetuzumab)

EXPERIMENTAL

Patients receive loncastuximab tesirine IV and mosunetuzumab IV on study. Patients also undergo PET/CT scan, biopsy, and collection of blood samples on study.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Loncastuximab Tesirine; Biological: Mosunetuzumab; Procedure: Positron Emission Tomography

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (oncastuximab tesirine, mosunetuzumab)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (oncastuximab tesirine, mosunetuzumab)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (oncastuximab tesirine, mosunetuzumab)

Loncastuximab Tesirine BIOLOGICAL

Given IV

Also known as: ADC ADCT-402, ADCT-402, Anti-CD19 PBD-conjugate ADCT-402, Loncastuximab Tesirine-lpyl, Zynlonta

Treatment (oncastuximab tesirine, mosunetuzumab)

Mosunetuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A, BTCT 4465A, BTCT-4465A, BTCT4465A, CD20/CD3 BiMAb BTCT4465A, Lunsumio, Mosunetuzumab-axgb, RG 7828, RG-7828, RG7828, RO7030816

Treatment (oncastuximab tesirine, mosunetuzumab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (oncastuximab tesirine, mosunetuzumab)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative.
• Assent, when appropriate, will be obtained per institutional guidelines.
• Be willing to provide tissue from a fresh core or excisional biopsy (performed as standard of care) of a tumor lesion prior to starting study therapy or from diagnostic tumor biopsies.
• If unavailable, exceptions may be granted with study principal investigator (PI) approval.
• Age: \>= 18 years.
• Eastern Cooperative Oncology Group (ECOG) =\< 2.
• Histologically confirmed diagnosis of diffuse large B-cell lymphoma or Follicular Lymphoma Grade 3B according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution. Subtypes of DLBCL including transformed indolent lymphomas (TIL) including Richter's Transformation, primary mediastinal large B-cell lymphoma (PMBCL), and high-grade B-cell lymphoma not otherwise specified (HGBCL-NOS) are eligible.
• Life expectancy \> 12 months.
• Histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma Grade 3B according to the WHO classification, with hematopathology review at the participating institution. Subtypes of DLBCL including transformed indolent lymphomas (TIL) including Richter's Transformation, primary mediastinal large B-cell lymphoma (PMBCL), and high-grade B-cell lymphoma not otherwise specified (HGBCL-NOS) are eligible.
• Relapsed or refractory disease after \>= 1 prior line of therapy (prior CD19-directed therapy and prior autologous stem cell transplant are allowed).
• Relapse at the time of study enrollment must have been confirmed histologically (with hematopathology review at the participating institution). Exceptions may be granted with study PI approval.
• Measurable disease by computerized tomography (CT) or positron emission tomography (PET)/CT scan with one or more sites of disease \>= 1.5 cm in longest dimension.
• Tumor must be positive for both CD19 and CD20 by immunohistochemistry after the most recent therapy.
• Fully recovered from the acute toxic effects (except alopecia) to =\< Grade 1 to prior anti-cancer therapy
• Without bone marrow involvement: Absolute neutrophil count (ANC) \>= 1,000/mm\^3.

You may not qualify if:

• Prior treatment with loncastuximab tesirine.
• Prior treatment with mosunetuzumab or other CD20-directed bispecific antibodies.
• Prior allogeneic stem cell transplantation.
• Prior use of any monoclonal antibody, radioimmunoconjugate or ADC within 2 weeks prior to Day 1 of protocol therapy.
• Treatment with any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 2 weeks or 5 half-lives of the drug, whichever is shorter, prior to Day 1 of protocol therapy.
• Treatment with radiotherapy within 2 weeks prior to Day 1 of protocol therapy.
• If patients have received radiotherapy within 4 weeks prior to prior to Day 1 of protocol therapy, patients must have at least one measurable lesion outside of the radiation field. Patients who have only one measurable lesion that was previously irradiated but subsequently progressed are eligible.
• Autologous stem cell transplantation (SCT) within 30 days prior to prior to Day 1 of protocol therapy.
• Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days prior to Day 1 of protocol therapy.
• Live vaccine within 30 days prior to Day 1 of protocol therapy.
• Concomitant investigational therapy.
• Treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents(e.g., immune checkpoint inhibitor therapies). Note: For certain prior treatments, such as CAR-T cell therapies, patients with prior immune-related Grade \>= 3 adverse events (e.g., CRS) may be allowed after discussion with and approval by the Study PI.
• Systemic steroid therapy or any other form of immunosuppressive therapy for lymphoma symptom control must be tapered down to =\< 20 mg/day prednisone or equivalent. Exceptions are:
• Inhaled or topical steroids
• Use of mineralocorticoids for management of orthostatic hypotension

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Biopsy; Specimen Handling; loncastuximab tesirine; Magnetic Resonance Spectroscopy

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Swetha Kambhampati

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 3, 2023
• First Posted: January 5, 2023
• Study Start: January 2, 2024
• Primary Completion: April 7, 2026
• Study Completion: April 7, 2026
• Last Updated: October 6, 2025

Record last verified: 2025-10

Locations

US (1)