A Study of Polatuzumab Vedotin and Glofitamab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma Within 12 Months After R-CHOP

Starting soon · Phase 2

Conditions studied: Diffuse Large B-cell Lymphoma

In brief

Patients with diffuse large B-cell lymphoma (DLBCL) who are primary refractory to first-line R-CHOP therapy or relapse within 12 months after R-CHOP have a poor prognosis and limited treatment options. Conventional salvage chemotherapy has limited efficacy, and CAR-T cell therapy may be limited by manufacturing time, accessibility, and patient condition. Therefore, an immediately available, chemotherapy-free treatment strategy that may reduce the cumulative toxicity of conventional cytotoxic chemotherapy is needed. Polatuzumab vedotin is a CD79b-targeted antibody-drug conjugate that delivers a cytotoxic agent to malignant B cells, and glofitamab is a CD20×CD3 bispecific antibody that activates T cells and induces immune-mediated antitumor activity. The combination of these two agents may provide complementary antitumor effects through direct tumor cell killing and T-cell-mediated immune response. This single-arm, open-label, phase 2 study will evaluate the efficacy and safety of polatuzumab vedotin in combination with glofitamab in patients with DLBCL who are primary refractory to or relapse within 12 months after first-line R-CHOP therapy. Approximately 47 participants will be enrolled. The primary endpoint is the complete response rate at the end of treatment, as assessed by the investigator according to Lugano 2014 criteria.

Key facts

Study ID

NCT07702851

Run by

Yonsei University

People needed

47

Starts

2026-09-01

Expected to finish

2030-08-31

Last updated by the study team

2026-07-14

Who can join

Age: 19 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically proven DLBCL
• Relapsed or refractory disease after first-line chemoimmunotherapy containing both rituximab and anthracycline A.Refractory disease defined as no complete remission to first-line therapy; subjects who are intolerant to first-line therapy are excluded
• Progressive disease (PD) as best response to first-line therapy
• Stable disease (SD) as best response after at least 4 cycles of first-line therapy
• Partial response (PR) as best response after at least 6 cycles, and biopsy-proven residual disease or disease B.Relapsed disease defined as complete remission to first-line therapy followed by biopsy- proven disease relapse ≤ 12 months of initiating first-line therapy
• Signed Informed Consent Form
• Age ≥ 19 years at the time of signing Informed Consent Form and willingness to comply with study protocol procedures
• Life expectancy ≥ 12 weeks
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2
• At least one bi-dimensionally measurable (≥ 1.5 cm) nodal lesion, or one bi-dimensionally measurable (≥ 1 cm) extranodal lesion, as measured on CT scan
• Negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test within 7 days prior to enrollment
• Negative HIV test at screening, with the following exception:
• i.Individuals with a positive HIV test at screening are eligible provided, prior to enrollment, they are stable on antiretroviral therapy, have a CD4 count ≥ 200/µL, and have an undetectable viral load.
• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agree to refrain from donating eggs, as defined below:
• i.Female participants must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 18 months after pretreatment with obinutuzumab, 2 months after the final dose of glofitamab, 9 months after the final dose of polatuzumab vedotin, and 3 months after the final dose of tocilizumab (as applicable), whichever is longer. Women must refrain from donating eggs during this same period ii.A female participant is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a female participant with tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.
• iii.Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• Hormonal contraceptive methods must be supplemented by a barrier method. iv.The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.
• For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agree to refrain from donating sperm, as defined below:
• i.With a female partner of childbearing potential or pregnant female partners, male participants must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 3 months after pretreatment with obinutuzumab, 2 months after the final dose of glofitamab, 6 months after the final dose of polatuzumab vedotin, or 2 months after the last dose of tocilizumab (as applicable), whichever is longer. Male participants must refrain from donating sperm during this same period.
• ii.The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.
• Adequate hematologic function (unless due to underlying disease, as established for example, by extensive bone marrow involvement or due to hypersplenism secondary to involvement of the spleen by LBCL per the investigator for which blood product transfusions are permitted) defined as follows:
• Hemoglobin ≥ 9.0 g/dL without packed RBC transfusion during 7 days before first treatment.
• ANC ≥1.0x109/L
• Platelet count ≥75 x 109/L
• Adequate renal function, defined as measured or estimated creatinine clearance ≥50 mL/min

You may not qualify if…

• Patients who meet any of the following criteria will be excluded from study entry:
• Contraindication to any of the individual components of glofitamab or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
• Prior solid organ transplantation
• Prior treatment with a regimen containing polatuzumab vedotin or glofitamab
• Prior treatment with systemic immunotherapeutic agents, including but not limited to, radio-immuno-conjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (mAbs) (e.g., anti-cytotoxic T lymphocyte associated protein 4, anti-PD-1, and anti-PD-L1) within 4 weeks or five half-lives of the drug, whichever is shorter
• Prior use of any monoclonal antibody for the purposes of treating cancer within 3 months of the start of Cycle 1
• Any investigational therapy for the purposes of treating cancer within 28 days prior to the start of Cycle 1
• Prior radiotherapy to the mediastinal/pericardial region(Radiotherapy to non-target lesion sites will be permitted.)
• Current Grade > 1 peripheral neuropathy
• Corticosteroid use > 50 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control i.Participants receiving corticosteroid treatment with ≤ 50 mg/day of prednisone or equivalent for reasons other than lymphoma symptom control (e.g., rheumatoid arthritis) must be documented to be on a stable dose of at least 4 weeks duration prior to the start of Cycle 1.
• Corticosteroid therapy for control of cancer symptoms or side effects of prior treatment (e.g., nausea or B-symptoms) is permitted
• The use of inhaled corticosteroids is permitted.
• The use of mineralocorticoids for management of orthostatic hypotension is permitted.
• The use of physiologic doses of corticosteroids for management of adrenal insufficiency is permitted.
• ii.Participants who require lymphoma symptom control during screening may receive steroids in the following manner:
• Up to 50 mg/day of prednisone or equivalent may be used for lymphoma symptom control during screening, including prior to finalization of staging (not included as part of pre-phase treatment).
• If glucocorticoid treatment is urgently required at higher doses for lymphoma symptom control prior to the start of study treatment, tumor assessments must be completed prior to initiation of > 30-100 mg/day of prednisone or equivalent. Prednisone > 30-100 mg/day or equivalent may be given for a maximum of 10-14 days as a pre-phase treatment. As part of the pre-phase treatment, vincristine may not be administered.
• History of other malignancy that could affect compliance with the protocol or interpretation of results:
• i.Participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to the study are eligible.
• ii.Participants with any malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for ≤ 2 years prior to enrollment are eligible.
• iii.Participants with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible.
• Significant or extensive history of cardiovascular disease such as New York Heart Association Class III or IV cardiac disease or Objective Assessment Class C or D, myocardial infarction within the last 3 months prior to the start of Cycle 1, unstable arrhythmias, or unstable angina
• Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
• Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis or neurodegenerative disease i.Participants with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurological deficits, as judged by the investigator, are allowed.
• Current or past history of CNS lymphoma

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