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

NCT07702851 | Not Yet Recruiting Phase 2

• 1 other identifier: 4-2026-0678
• Study Type: interventional
• Target: 47
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  At the end of treatment (EOT), up to approximately 36 weeks after the first dose.

Secondary Outcomes (7)

• Overall response rate

  From the first dose through the end of treatment (EOT), up to approximately 36 weeks.

• Duration of response

  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

  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

  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

  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.

Study Arms (1)

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.

Drug: Polatuzumab vedotin, Glofitamab

Interventions

Polatuzumab vedotin, Glofitamab DRUG

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.

Polatuzumab vedotin, Glofitamab

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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:

Sponsors & Collaborators

• Yonsei University: lead

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Recurrence

Interventions

polatuzumab vedotin; glofitamab

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

JIN SEOK KIM, Professor

CONTACT

+82-02-2228-4242; HEMAKIM@yuhs.ac

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: July 6, 2026
• First Posted: July 14, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 31, 2030
• Study Completion (Estimated): August 31, 2030
• Last Updated: July 14, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share