NCT07231250

Glofitamab Plus Polatuzumab Vedotin and Zuberitamab in Patients With Newly Diagnosed Diffuse Large B-cell Lymphoma

Glofitamab Plus Polatuzumab Vedotin and Zuberitamab in Patients With Newly Diagnosed Diffuse Large B-cell Lymphoma: A Multicenter Phase II Study

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Li Zhiming · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multi-center, phase II, prospective study. The main purpose of study is to evaluate the efficacy and safety of Glofitamab plus Polatuzumab vedotin and Zuberitamab in patients with newly diagnosed diffuse large B-cell lymphoma.

Detailed description

Nearly 1/3 of newly diagnosed DLBCL patients are over 75 years old, with a median age of 66. The number and proportion of patients unable to tolerate conventional immunochemotherapy continue to rise. Serious long-term toxicities associated with chemotherapy (e.g., reproductive effects, secondary malignancies) have created substantial clinical demand for first-line chemotherapy-free regimens. There is an urgent need for more clinical trials to explore the feasibility of chemo-free or chemo-light regimens in previously untreated DLBCL. The Smart Stop study from MD Anderson is currently exploring chemotherapy-free, response-adapted therapy based on LTRA (Lymphoma Treatment Response Assessment) protocols. Meanwhile, the MOLTO study demonstrated that atezolizumab combined with venetoclax and obinutuzumab provides effective and well-tolerated treatment for previously untreated transformed DLBCL. This evidence above supports chemo-free or chemo-light regimens as a promising new direction for investigation in previously untreated DLBCL. Early data suggest that Glofit + Pola-R-CHP in 1L DLBCL has promising efficacy and a similar safety profile to Pola-R-CHP and Glofit + R-CHOP. This is a multi-center, phase II, prospective study. The main purpose of study is to evaluate the efficacy and safety of Glofitamab plus Polatuzumab vedotin and Zuberitamab in patients with newly diagnosed diffuse large B-cell lymphoma. After receiving 3 cycles of Glofitamab plus Polatuzumab vedotin and Zuberitamab（Anti-CD20 Monoclonal Antibody）, patients were treated with Glofitamab plus Polatuzumab vedotin and Zuberitamab for 5 cycles if CR or Glofitamab plus Polatuzumab vedotin and Zuberitamab-CHP for 6 cycles if PR/SD based on iPET status. The primary efficacy endpoint is CR rate at C4D1.

Conditions

• DLBCL - Diffuse Large B Cell Lymphoma
• Chemo-free Therapy
• Bispecific Antibody

Interventions

Type	Name	Description
DRUG	Glofitamab; Polatuzumab vedotin; Zuberitamab; Cyclophosphamide; Doxorubicin; Prednisone	Step-up cycle (cycle 1) will comprise intravenous (i.v.) application of obinutuzumab 1,000 mg on D1, followed by i.v. application of polatuzumab vedotin 1.8 mg/kg on D2 and i.v. application of glofitamab in escalating doses of 2.5 mg on D8 and 10 mg on D15. Target dose phase (cycle 2-3) will comprise polatuzumab vedotin 1.8 mg/kg, i.v., glofitamab 30 mg i.v. and Zuberitamab 375mg/m2 i.v. on D1 and repeated Q3W. Adaptive treatment phase (cycle 4-9) will include two arms with dose cycle guided by PET/CT after C3: i.) If CR, it will comprise polatuzumab vedotin 1.8 mg/kg, i.v.(C4-6) on D1, glofitamab 30 mg i.v. (C4-8) on D2 and Zuberitamab 375mg/m2 i.v. (C4-8) on D1 and repeated Q3W. ii.) if PR or SD, it will comprise polatuzumab vedotin 1.8 mg/kg, i.v .(C4-6) on D1, glofitamab 30 mg i.v. (C4-8) on D8, Zuberitamab-CHP\[Zuberitamab 375mg/m2 i.v., cyclophosphamide i.v., doxorubicin i.v., and prednisone p.o. (C4-9)\] on D1 and repeated Q3W.

Timeline

• Start date: 2026-01-15
• Primary completion: 2026-09-15
• Completion: 2028-09-15
• First posted: 2025-11-17
• Last updated: 2025-11-19

Locations

1 site across 1 country: China