Diffuse Large B-cell LymphomaPhase 2NCT07702851
A Study of Polatuzumab Vedotin and Glofitamab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma Within 12 Months After R-CHOP
A Phase 2 study testing Polatuzumab vedotin, Glofitamab in people with Diffuse Large B-cell Lymphoma, run by Yonsei University.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Diffuse Large B-cell Lymphoma
- What is being tested?
- Polatuzumab vedotin, Glofitamab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2026to 31 Aug 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 25Show fewer
- 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
Who cannot join
- 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
Show all 52Show fewer
- 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
- Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
- Current or past history of Waldenström macroglobulinemia
- History or presence of an abnormal ECG that is clinically significant in the investigator's opinion
- Patients with known or suspected active infection, or reactivation of a latent infection, whether bacterial, viral (including, but not limited to, SARS-Cov-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis B, and hepatitis C), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 4 weeks of dosing
- History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows:
- i.Grade ≥ 3 adverse events with the exception of Grade 3 endocrinopathy managed with replacement therapy.
- ii.Grade 1/2 adverse events that did not resolve to baseline after treatment discontinuation.
- 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's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis i.Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
- ii.Participants with a history of disease-related immune thrombocytopenic purpura or autoimmune hemolytic anemia may be eligible for this study.
- iii.Participants with controlled Type I diabetes mellitus who are on an insulin regimen are eligible for the study.
- iv.Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible (e.g., participants with psoriatic arthritis are excluded) if all the following conditions are met:
- Rash covers < 10% of body surface area.
- Disease is well controlled for the last 12 months and requires only low-potency topical corticosteroids.
- Clinically significant liver disease, including active viral or other hepatitis or cirrhosis
- Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
- Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying lymphoma):
- INR or PT >1.5 Xupper limit of normal (ULN) in the absence of therapeutic anticoagulation.
- PTT or aPTT > 1.5 XULN in the absence of a lupus anticoagulant.
- Serum AST and ALT ≥ 2.5 XULN
- Total bilirubin ≥ 1.5XULN Participants with documented Gilbert disease may be enrolled if total bilirubin is ≤ 3.0XULN
- Live, attenuated vaccine within 4 weeks before study treatment infusion on Day 1 of Cycle 1 or anticipation that such a live, attenuated vaccine will be required during the study. Live vaccines during the study and until participants B cells recover, are prohibited Influenza vaccination should be given during influenza season only. Participants must not receive live, attenuated influenza vaccine at any time during the study treatment period.
- Suspected active or latent tuberculosis (as confirmed by a positive interferon-gamma release assay)
- Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HBsAg] serology) Participants with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus (HBV) DNA is undetectable at the time of screening. Such participants must be willing to undergo HBV DNA testing on Day 1 of every cycle and every 3 months for at least 12 months after the final cycle of study treatment and appropriate antiviral therapy as indicated.
- Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing) Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
- Participants with a history of progressive multifocal leukoencephalopathy
- Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 18 months after pretreatment with obinutuzumab or 2 months after the final dose of glofitamab, whichever is longer
- Positive SARS-CoV-2 test within 7 days prior to enrollment. Rapid antigen test result is also acceptable
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A PROSPECTIVE MULTICENTER PHASE 2 STUDY OF THE CHEMOTHERAPY-FREE COMBINATION OF POLATUZUMAB VEDOTIN AND GLOFITAMAB IN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA WITHIN 12 MONTHS OF R-CHOP TREATMENT
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.
Read the detailed description
This is a multicenter, single-arm, open-label, phase 2 study designed to evaluate the efficacy and safety of polatuzumab vedotin in combination with glofitamab in 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 therapy.
Approximately 47 participants will be enrolled at approximately seven study sites in Korea, allowing for an approximately 10% dropout rate to secure 42 efficacy-evaluable participants. The planned enrollment period is approximately 24 months. Participants will be followed for at least 12 months after the end of treatment, and the total study duration is expected to be approximately 4 years.
Treatment will be administered for a fixed duration of up to 12 cycles, with each cycle defined as 21 days. The treatment period consists of two parts.
Part A includes Cycles 1 through 6, during which participants will receive obinutuzumab pretreatment followed by combination therapy with polatuzumab vedotin and glofitamab. Obinutuzumab 1000 mg will be administered once by intravenous infusion on Cycle 1 Day 1. Polatuzumab vedotin 1.8 mg/kg will be administered by intravenous infusion on Cycle 1 Day 2 and then on Day 1 of each cycle from Cycle 2 through Cycle 6 at 21-day intervals. Glofitamab will be administered using step-up dosing: 2.5 mg by intravenous infusion on Cycle 1 Day 8, 10 mg by intravenous infusion on Cycle 1 Day 15, and 30 mg by intravenous infusion on Day 1 of each cycle from Cycle 2 through Cycle 6.
Part B includes Cycles 7 through 12, during which participants will receive glofitamab monotherapy. Glofitamab 30 mg will be administered by intravenous infusion on Day 1 of each 21-day cycle.
Disease response will be assessed using PET-CT, or contrast-enhanced CT if PET-CT cannot be performed, at Week 9, Week 18, Week 36, and at the end of treatment, based on Cycle 1 Day 1. Response will be evaluated according to Lugano 2014 criteria.
The primary endpoint is the complete response rate at the end of treatment, as assessed by the investigator according to Lugano 2014 criteria. Secondary endpoints include overall response rate, duration of response, progression-free survival, overall survival, duration of complete response, time to first objective response, and safety. Exploratory analyses will evaluate ctDNA-based minimal residual disease and immune cell profiling in relation to clinical response and long-term outcomes.
To reduce the risk of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, risk mitigation measures including obinutuzumab pretreatment, step-up dosing of glofitamab, and premedication will be implemented according to the protocol.
- Conditions
- Diffuse Large B-cell Lymphoma
- Being tested
- Polatuzumab vedotin, Glofitamab
- Keywords
- Diffuse large B-cell lymphoma, Relapsed or refractory DLBCL, Polatuzumab vedotin, Glofitamab, Phase 2, Complete response rate, Lugano 2014
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Polatuzumab vedotin, GlofitamabDrug
Participants will receive fixed-duration treatment with polatuzumab vedotin in combination with glofitamab. Obinutuzumab 1000 mg will be administered once by intravenous infusion on Cycle 1 Day 1 as pretreatment before glofitamab administration. Polatuzumab vedotin 1.8 mg/kg will be administered by intravenous infusion on Cycle 1 Day 2 and then on Day 1 of each cycle from Cycle 2 through Cycle 6. Glofitamab will be administered by intravenous infusion using step-up dosing: 2.5 mg on Cycle 1 Day 8, 10 mg on Cycle 1 Day 15, and 30 mg on Day 1 of each cycle from Cycle 2 through Cycle 12. Each cycle is 21 days.
| Study group | Role | What they receive |
|---|---|---|
| Polatuzumab vedotin, Glofitamab | Experimental | Participants will receive fixed-duration treatment with polatuzumab vedotin in combination with glofitamab, followed by glofitamab monotherapy. Treatment will be administered in 21-day cycles for up to 12 cycles. In Part A, corresponding to Cycles 1 through 6, participants will receive obinutuzumab pretreatment, polatuzumab vedotin, and glofitamab. In Part B, corresponding to Cycles 7 through 12, participants will receive glofitamab monotherapy. Receives: Drug: Polatuzumab vedotin, Glofitamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate at the end of treatment
Complete response rate is defined as the proportion of participants who achieve complete response at the end of treatment, as assessed by the investigator according to Lugano 2014 criteria based on PET-CT.
Measured: At the end of treatment (EOT), up to approximately 36 weeks after the first dose.
Secondary outcomes (7)
Overall response rate
EOT ORR is defined as the proportion of participants achieving CR or PR at EOT.
Measured: From the first dose through the end of treatment (EOT), up to approximately 36 weeks.
Duration of response
DOR is defined as the time from the first documented objective response to disease progression or death from any cause.
Measured: From the first documented objective response until disease progression or death from any cause, assessed when all enrolled participants have completed at least 12 months of follow-up after EOT.
Progression-free survival
PFS is defined as the time from the first dose to disease progression or death from any cause.
Measured: From the first dose until disease progression or death from any cause, whichever occurs first, assessed when all enrolled participants have completed at least 12 months of follow-up after EOT.
Overall survival
OS is defined as the time from the first dose to death from any cause.
Measured: From the first dose until death from any cause, assessed when all enrolled participants have completed at least 12 months of follow-up after EOT.
Duration of complete response
DOCR is defined as the time from the first documented complete response to disease progression or death from any cause.
Measured: From the first documented complete response until disease progression or death from any cause, assessed when all enrolled participants have completed at least 12 months of follow-up after EOT.
Time to first objective response
TFOR is defined as the time from the first dose to the first documented objective response.
Measured: From the first dose until the first documented objective response, up to approximately 36 weeks.
Safety
Safety will be assessed based on the incidence, nature, frequency, severity, and timing of adverse events (AEs) and serious adverse events (SAEs), graded according to NCI CTCAE v5.0.
Measured: From the first dose through 30 days after the last dose of study treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2026
- Study start1 Sep 2026 (estimated)
- Primary completion31 Aug 2030 (estimated)
- Study completion31 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B-cell LymphomaStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07702851
- Sponsor's protocol ID
- 4-2026-0678
- Status last verified
- Jul 2026
- First submitted
- 6 Jul 2026
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PROSPECTIVE MULTICENTER PHASE 2 STUDY OF THE CHEMOTHERAPY-FREE COMBINATION OF POLATUZUMAB VEDOTIN AND GLOFITAMAB IN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA WITHIN 12 MONTHS OF R-CHOP TREATMENT
- ClinicalTrials.gov ID
- NCT07702851
- Acronym / sponsor ID
- 4-2026-0678
- Conditions
- Diffuse Large B-cell Lymphoma
- Keywords
- Diffuse large B-cell lymphoma, Relapsed or refractory DLBCL, Polatuzumab vedotin, Glofitamab, Phase 2, Complete response rate, Lugano 2014
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 47 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 31 Aug 2030 (estimated)
- Study completion
- 31 Aug 2030 (estimated)
- First posted
- 14 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multicenter, single-arm, open-label, phase 2 study designed to evaluate the efficacy and safety of polatuzumab vedotin in combination with glofitamab in 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 therapy.
Approximately 47 participants will be enrolled at approximately seven study sites in Korea, allowing for an approximately 10% dropout rate to secure 42 efficacy-evaluable participants. The planned enrollment period is approximately 24 months. Participants will be followed for at least 12 months after the end of treatment, and the total study duration is expected to be approximately 4 years.
Treatment will be administered for a fixed duration of up to 12 cycles, with each cycle defined as 21 days. The treatment period consists of two parts.
Part A includes Cycles 1 through 6, during which participants will receive obinutuzumab pretreatment followed by combination therapy with polatuzumab vedotin and glofitamab. Obinutuzumab 1000 mg will be administered once by intravenous infusion on Cycle 1 Day 1. Polatuzumab vedotin 1.8 mg/kg will be administered by intravenous infusion on Cycle 1 Day 2 and then on Day 1 of each cycle from Cycle 2 through Cycle 6 at 21-day intervals. Glofitamab will be administered using step-up dosing: 2.5 mg by intravenous infusion on Cycle 1 Day 8, 10 mg by intravenous infusion on Cycle 1 Day 15, and 30 mg by intravenous infusion on Day 1 of each cycle from Cycle 2 through Cycle 6.
Part B includes Cycles 7 through 12, during which participants will receive glofitamab monotherapy. Glofitamab 30 mg will be administered by intravenous infusion on Day 1 of each 21-day cycle.
Disease response will be assessed using PET-CT, or contrast-enhanced CT if PET-CT cannot be performed, at Week 9, Week 18, Week 36, and at the end of treatment, based on Cycle 1 Day 1. Response will be evaluated according to Lugano 2014 criteria.
The primary endpoint is the complete response rate at the end of treatment, as assessed by the investigator according to Lugano 2014 criteria. Secondary endpoints include overall response rate, duration of response, progression-free survival, overall survival, duration of complete response, time to first objective response, and safety. Exploratory analyses will evaluate ctDNA-based minimal residual disease and immune cell profiling in relation to clinical response and long-term outcomes.
To reduce the risk of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, risk mitigation measures including obinutuzumab pretreatment, step-up dosing of glofitamab, and premedication will be implemented according to the protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Polatuzumab vedotin, Glofitamab | Experimental | Drug: Polatuzumab vedotin, GlofitamabParticipants will receive fixed-duration treatment with polatuzumab vedotin in combination with glofitamab, followed by glofitamab monotherapy. Treatment will be administered in 21-day cycles for up to 12 cycles. In Part A, corresponding to Cycles 1 through 6, participants will receive obinutuzumab pretreatment, polatuzumab vedotin, and glofitamab. In Part B, corresponding to Cycles 7 through 12, participants will receive glofitamab monotherapy. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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
- 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
Key exclusion criteria (52 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Polatuzumab vedotin, GlofitamabParticipants will receive fixed-duration treatment with polatuzumab vedotin in combination with glofitamab. Obinutuzumab 1000 mg will be administered once by intravenous infusion on Cycle 1 Day 1 as pretreatment before glofitamab administration. Polatuzumab vedotin 1.8 mg/kg will be administered by intravenous infusion on Cycle 1 Day 2 and then on Day 1 of each cycle from Cycle 2 through Cycle 6. Glofitamab will be administered by intravenous infusion using step-up dosing: 2.5 mg on Cycle 1 Day 8, 10 mg on Cycle 1 Day 15, and 30 mg on Day 1 of each cycle from Cycle 2 through Cycle 12. Each cycle is 21 days. | Drug | Polatuzumab vedotin, Glofitamab |
Primary outcome
Complete response rate at the end of treatment
Time frame: At the end of treatment (EOT), up to approximately 36 weeks after the first dose.
Complete response rate is defined as the proportion of participants who achieve complete response at the end of treatment, as assessed by the investigator according to Lugano 2014 criteria based on PET-CT.
7 secondary outcomes
Overall response rate
Time frame: From the first dose through the end of treatment (EOT), up to approximately 36 weeks.
Duration of response
Time frame: From the first documented objective response until disease progression or death from any cause, assessed when all enrolled participants have completed at least 12 months of follow-up after EOT.
Progression-free survival
Time frame: From the first dose until disease progression or death from any cause, whichever occurs first, assessed when all enrolled participants have completed at least 12 months of follow-up after EOT.
Overall survival
Time frame: From the first dose until death from any cause, assessed when all enrolled participants have completed at least 12 months of follow-up after EOT.
Duration of complete response
Time frame: From the first documented complete response until disease progression or death from any cause, assessed when all enrolled participants have completed at least 12 months of follow-up after EOT.
Time to first objective response
Time frame: From the first dose until the first documented objective response, up to approximately 36 weeks.
Safety
Time frame: From the first dose through 30 days after the last dose of study treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
- Individual participant dataSharing planned: No
Related trials for Diffuse Large B-cell Lymphoma
Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
Active, not recruitingEarly Phase 1
Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma
B-ALL, DLBCL
Not yet recruitingPhase 2
The CARDIOPROTECT Trial
Diffuse Large B-cell Lymphoma (DLBCL), Cardiotoxicity
Not yet recruitingPhase 2
QLS4131 Plus Isa-V-CHOP in Newly Diagnosed, HIV-Negative PBL: A Single-Center, Single-Arm, Phase II Study
Plasmablastic Lymphoma
RecruitingPhase 2
Testing the Effectiveness of a Combination Targeted Therapy (ViPOR) for Patients With Relapsed and/or Refractory Aggressive B-cell Lymphoma
High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements, Recurrent Diffuse Large B-Cell Lymphoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Polatuzumab vedotin, Glofitamab in people with Diffuse Large B-cell Lymphoma, run by Yonsei University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 52 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 14 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact JIN SEOK KIM, Professor (+82-02-2228-4242, HEMAKIM@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete response rate at the end of treatment (time frame: At the end of treatment (EOT), up to approximately 36 weeks after the first dose.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2026.