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.
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
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
Single group
Polatuzumab vedotin, Glofitamab
DrugParticipants 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.
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.
Overall response rate
EOT ORR is defined as the proportion of participants achieving CR or PR at EOT.
Duration of response
DOR is defined as the time from the first documented objective response to disease progression or death from any cause.
Progression-free survival
PFS is defined as the time from the first dose to disease progression or death from any cause.
Overall survival
OS is defined as the time from the first dose to death from any cause.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
