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Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 2INTERVENTIONAL

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

A Phase 2 Study of Loncastuximab Tesirine Plus Mosunetuzumab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma

Loncastuximab Tesirine and Mosunetuzumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma (NCT05672251) is a Phase 2 interventional studying Recurrent Diffuse Large B-Cell Lymphoma and Recurrent Grade 3b Follicular Lymphoma, sponsored by City of Hope Medical Center. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Recurrent Diffuse Large B-Cell Lymphoma and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 36 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: - Documented willing to sign a consent form 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. - diagnosed by tissue sample (biopsy-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. - diagnosed by tissue sample (biopsy-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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * 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. * (G-CSF is allowed to reach ANC requirement). * With bone marrow involvement: no minimum ANC requirement. * (G-CSF is allowed to reach ANC requirement). * Platelets \>= 75,000/mm\^3. * Total bilirubin =\< 1.5 X upper limit of normal (ULN). * If hepatic involvement by lymphoma, or Gilbert's disease: =\< 3X ULN. * Aspartate aminotransferase (AST) =\< 2.5 x ULN. * If hepatic involvement by lymphoma: AST =\< 5 x ULN. * Alanine aminotransferase (ALT) =\< 2.5 x ULN. * If hepatic involvement by lymphoma: ALT =\< 5 x ULN . * Creatinine clearance of \>= 40 mL/min per 24 hour urine test or the Cockcroft-Gault formula * If not receiving anticoagulants: International Normalized Ratio (INR) OR Prothrombin (PT) =\< 1.5 x ULN. * If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants. * If not receiving anticoagulants: Activated Partial Thromboplastin Time (aPTT) =\< 1.5 x ULN * If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants. * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Agreement by females of childbearing potential to abstain from heterosexual intercourse or use two adequate method of birth control, including at least 1 method with a failure rate of \< 1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period (including periods of treatment interruption), until 3 months after the final dose mosunetuzumab and 9 months after the last dose of loncastuximab tesirine. Women must refrain from donating eggs during this same period. Agreement by males to abstain from heterosexual intercourse or use a condom with female partners of childbearing potential or pregnant female partners during the treatment period and for 3 months after the final dose of mosunetuzumab and 6 months after the last dose of loncastuximab tesirine. Men must refrain from donating sperm during this same period. * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only) with no identified cause other than menopause. * Examples of non-hormonal contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, established and proper use of progestogen only hormonal contraceptives that inhibit ovulation, hormone releasing intrauterine devices, and copper intrauterine devices. Barrier methods must always be supplemented with the use of a spermicide. Note: Combined oral contraceptives are not recommended. Exclusion Criteria: * 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 * Use of physiologic doses of corticosteroids for management of adrenal insufficiency * Known hypersensitivity to biopharmaceutical produced in chinese hamster ovary (CHO) cells or history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents. * Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath). * History of solid organ transplantation. * History of progressive multifocal leukoencephalopathy (PML). * Known or suspected history of hemophagocytic lymphohistiocytosis (HLH). * Clinically significant uncontrolled illness. * Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment. * Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with past HBV infection (defined as negative hepatitis B surface antigen \[HBsAg\] and positive hepatitis B core antibody \[HBcAb\]) are eligible if HBV deoxyribonucleic acid (DNA) is undetectable. Patients who are positive for HCV antibody are eligible if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). Testing to be done only in patients suspected of having infections or exposures. * Known active human immunodeficiency virus (HIV) infection. Subjects who have an undetectable or unquantifiable HIV viral load with CD4 \> 200 and are on HAART medication are allowed. Testing to be done only in patients suspected of having infections or exposures. * Known or suspected chronic active Epstein-Barr virus (EBV) infection. * Known active central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement. * History of erythrema multiforme, Grade \>= 3 rash, or blistering following prior treatment with immunomodulatory derivatives. * Symptomatic cardiac disease (including symptomatic ventricular dysfunction, symptomatic coronary artery disease, and symptomatic arrhythmias), cerebrovascular event/stroke or myocardial infarction within the past 6 months. * Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis. * Active autoimmune disease requiring treatment. * History of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. * Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. * Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. * Patients with a history of disease-related immune thrombocytopenic purpura, autoimmune hemolytic anemia, or other stable autoimmune diseases may be eligible. * Recent major surgery (within 4 weeks) prior to start of protocol therapy, other than for diagnosis. * History of another primary malignancy that has not been in remission for at least 2 years, with the following exceptions: * Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease * Adequately treated in situ carcinomas (e.g. cervical, esophageal) without evidence of disease * Asymptomatic prostate cancer managed with a watch-and-wait strategy * If the malignancy is expected to not require any treatment for at least 2 years (this exception should be discussed with the study PI). * Females only: Pregnant or breastfeeding. * Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures. * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Treatments Being Tested

PROCEDURE

Biopsy

Undergo biopsy

PROCEDURE

Biospecimen Collection

Undergo collection of blood samples

PROCEDURE

Computed Tomography

Undergo PET/CT

BIOLOGICAL

Loncastuximab Tesirine

Given IV

BIOLOGICAL

Mosunetuzumab

Given IV

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

City of Hope Medical Center
Duarte, California, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT05672251), the sponsor (City of Hope Medical Center), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT05672251 clinical trial studying?

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 tesi… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT05672251?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT05672251?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT05672251. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT05672251. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-26 · Data from ClinicalTrials.gov.