Mosunetuzumab + Polatuzumab Vedotin for Follicular Lymphoma
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: City of Hope Medical Center
Must not be taking: Immunosuppressants, Anticancer agents
Disqualifiers: Active infection, Autoimmune disease, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This phase II trial tests how well mosunetuzumab and polatuzumab vedotin works in treating patients with grade 1-3a follicular lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Polatuzumab vedotin is a monoclonal antibody, polatuzumab, linked to a toxic agent called vedotin. Polatuzumab attaches to CD79B positive cancer cells in a targeted way and delivers vedotin to kill them. Giving mosunetuzumab and polatuzumab vedotin may kill more cancer cells in patients with relapsed or refractory grade 1-3a follicular lymphoma.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, if you are on systemic immunosuppressive therapy, it must be reduced to a low dose before starting the trial. It's best to discuss your specific medications with the study team.
What data supports the effectiveness of the drugs Mosunetuzumab and Polatuzumab Vedotin for treating follicular lymphoma?
Polatuzumab Vedotin has shown significant activity in treating follicular lymphoma, as seen in trials where it was combined with other drugs like obinutuzumab and lenalidomide. Mosunetuzumab has been conditionally approved in the EU for treating relapsed or refractory follicular lymphoma, indicating its potential effectiveness.
12345Is the combination of Mosunetuzumab and Polatuzumab Vedotin safe for humans?
Polatuzumab Vedotin, also known as Polivy, has been studied in combination with other drugs for treating certain types of lymphoma, and it has shown a low risk of causing immune reactions in patients. It has been approved for use in some lymphoma treatments, indicating it is generally considered safe when used as directed.
14678How is the drug combination of Mosunetuzumab and Polatuzumab Vedotin unique for treating follicular lymphoma?
This drug combination is unique because Mosunetuzumab is a bispecific antibody that engages T-cells to target cancer cells, while Polatuzumab Vedotin is an antibody-drug conjugate that delivers a toxic agent directly to B-cells. Together, they offer a novel approach by combining two different mechanisms to attack the cancer more effectively.
12389Eligibility Criteria
This trial is for patients with grade 1-3a follicular lymphoma that has either relapsed or hasn't responded to previous treatments. Participants should have a type of cancer that the drugs used in this study can target.Inclusion Criteria
Documented informed consent of the participant and/or legally authorized representative
I am 18 years old or older.
I have recovered from side effects of previous cancer treatments.
+13 more
Exclusion Criteria
I do not have active viral infections like HBV, HCV, HIV, or chronic EBV.
I have heart, liver, autoimmune conditions, or had major surgery recently.
I am not on any immune-suppressing drugs, with certain exceptions.
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Patients receive polatuzumab vedotin IV and mosunetuzumab SC in cycles every 21 days for up to 6-17 cycles
18-51 weeks
Visits every 21 days for each cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment
36 months
Follow-up at 30 days post-treatment and then for 3 years
Participant Groups
The effectiveness of mosunetuzumab and polatuzumab vedotin is being tested on patients with specific types of follicular lymphoma. The trial involves various diagnostic tests like CT, PET, MRI scans, and questionnaires to monitor progress.
1Treatment groups
Experimental Treatment
Group I: Treatment (mosunetuzumab, polatuzumab vedotin)Experimental Treatment7 Interventions
Patients receive polatuzumab vedotin IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mosunetuzumab SC on days 1, 8 and 15 of cycle 1 and day 1 of remaining cycles. Cycles repeat every 21 days for up to 8-17 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and CT, PET/CT, or MRI throughout the study.
Mosunetuzumab is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Lunsumio for:
- Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
🇺🇸 Approved in United States as Lunsumio for:
- Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
City of Hope Orange County Lennar Foundation Cancer CenterIrvine, CA
City of Hope Medical CenterDuarte, CA
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Who Is Running the Clinical Trial?
City of Hope Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Profile of Polatuzumab Vedotin in the Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma: A Brief Report on the Emerging Clinical Data. [2022]Polatuzumab vedotin is an anti-CD79b antibody conjugated to monomethyl auristatin E that has shown significant clinical activity in follicular and diffuse large B-cell lymphoma (DLBCL) and is currently FDA-approved in combination with bendamustine and rituximab for patients with relapsed/refractory DLBCL. This review article summarizes data from clinical trials of polatuzumab and discusses its current role and future directions in the treatment of patients with B-cell non-Hodgkin lymphoma.
Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. [2022]Obinutuzumab with polatuzumab vedotin or lenalidomide showed tolerability and activity in phase 1b/2 trials that recruited patients with relapsed or refractory follicular lymphoma. We aimed to examine whether the novel polatuzumab vedotin-obinutuzumab-lenalidomide (Pola-G-Len) combination might enhance antitumour response in patients with relapsed or refractory follicular lymphoma.
Mosunetuzumab: First Approval. [2022]Mosunetuzumab (Lunsumio®), an anti-CD20/CD3 T-cell engaging bispecific antibody, is being developed by Roche for the treatment of relapsed or refractory follicular lymphoma. Mosunetuzumab was recently conditionally approved in the EU for the treatment of relapsed or refractory follicular lymphoma in adults who have received at least two prior systemic therapies. This article summarizes the milestones in the development of mosunetuzumab leading to this first approval for relapsed or refractory follicular lymphoma.
Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. [2023]Polatuzumab vedotin, an antibody-drug conjugate targeting the CD79b component of the B-cell receptor, has demonstrated activity as a single agent and in combination with rituximab in relapsed or refractory diffuse large B-cell lymphoma. In this study, we evaluated the safety and preliminary activity of polatuzumab vedotin in combination with rituximab or obinutuzumab and cyclophosphamide, doxorubicin, and prednisone (CHP) in patients with previously untreated diffuse large B-cell lymphoma.
A multicenter retrospective study of polatuzumab vedotin in patients with large B-cell lymphoma after CAR T-cell therapy. [2023]Polatuzumab vedotin (PV) is an antibody-drug conjugate targeting CD79b that is approved for patients with relapsed/refractory large B-cell lymphoma (LBCL). Patients who relapse after chimeric antigen receptor (CAR) T-cell therapy were not included in the registration study, and reports of PV use after CAR T cells are limited. This multicenter retrospective analysis included patients with LBCL who relapsed or progressed after CAR T-cell therapy and subsequently received PV with or without rituximab and bendamustine between July 2019 and May 2021. Response to treatment and progression were assessed based on the 2014 Lugano criteria. Fifty-seven patients were included in the study: 18 (32%) patients were primary refractory to CAR T-cell therapy, and 34 (60%) patients received PV-based therapy immediately after CAR T-cell therapy. PV was combined with rituximab in 54 (95%) patients and administered with bendamustine in 35 (61%) patients. A response was achieved in 25 (44%) patients, including complete remission in 8 (14%). No significant association between baseline characteristics and response was observed. After a median follow-up of 47 weeks (95% confidence interval [CI], 40-54), 46 (81%) patients had disease progression or died, and the median progression-free survival was 10 weeks (95% CI, 5-15). On a multivariate analysis, bone marrow involvement (hazard ratio, 5.2; 95% CI, 1.8-15; P = .003) and elevated lactate dehydrogenase levels (hazard ratio, 5.0; 95% CI, 1.4-16; P = .01) were associated with shorter progression-free survival. Studies aimed at better characterizing the intrinsic mechanism of resistance and identifying optimal consolidation strategies for these patients are warranted.
Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. [2023]Polatuzumab vedotin, marketed under the trade name POLIVY®, is a CD79b-targeted antibody-drug conjugate that preferentially delivers a potent anti-mitotic agent (monomethyl auristatin E) to B cells, resulting in anti-cancer activity against B-cell malignancies. In 2019, polatuzumab vedotin in combination with rituximab and bendamustine was approved by the United States Food and Drug Administration for the treatment of adult patients with diffuse large B-cell lymphoma who have received at least two prior therapies. Recent Health Authority guidance recommendations for submitting an Integrated Summary of Immunogenicity were followed including a comprehensive immunogenicity risk assessment, bioanalytical strategy, and immunogenicity data to support the registration of polatuzumab vedotin. Key components of the polatuzumab vedotin Integrated Summary of Immunogenicity and data are presented. Validated semi-homogeneous bridging enzyme-linked immunosorbent assays were used to detect anti-drug antibodies (ADA) to polatuzumab vedotin and characterize the immune response in patients with non-Hodgkin's lymphoma. The overall incidence of ADA observed for polatuzumab vedotin was low across seven clinical trials. The low incidence of ADA is likely due to the mechanism of action of polatuzumab vedotin that involves targeting and killing of B cells, thereby limiting the development to plasma cells and ADA secretion. Furthermore, patients are co-medicated with rituximab, which also targets B cells and results in B-cell depletion. Therefore, the immunogenicity risk is considered low and not expected to impact the polatuzumab vedotin benefit/risk profile.
Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma. [2020]The phase Ib/II open-label study (NCT01992653) evaluated the antibody-drug conjugate polatuzumab vedotin (pola) plus rituximab/obinutuzumab, cyclophosphamide, doxorubicin, and prednisone (R/G-CHP) as first-line therapy for B-cell non-Hodgkin lymphoma (B-NHL). We report the pharmacokinetics (PK) and drug-drug interaction (DDI) for pola.
Polatuzumab Vedotin: First Global Approval. [2023]Polatuzumab vedotin (polatuzumab vedotin-piiq; Polivy™) is an antibody-drug conjugate comprising a monoclonal antibody against CD79b (a B cell receptor component) covalently conjugated to the anti-mitotic cytotoxic agent monomethyl auristatin (MMAE) via a cleavable linker. After binding to CD79b on the B-cell surface, polatuzumab vedotin is internalized and the linker is cleaved, releasing MMAE into the cell, where it inhibits division and induces apoptosis. Polatuzumab vedotin is being developed by Genentech (a subsidiary of Roche) for the treatment of haematological malignancies. In June 2019, the US FDA granted accelerated approval to polatuzumab vedotin, in combination with bendamustine plus rituximab, for the treatment of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who have received at least two prior therapies. Use of the compound in combination with bendamustine plus rituximab is also under regulatory review for relapsed/refractory DLBCL in the EU and is in ongoing phase 1b/2 development in this setting or relapsed/refractory follicular lymphoma (FL) in several countries. Various other polatuzumab vedotin combination therapy regimens are also in phase 1b/2 development for relapsed/refractory non-Hodgkin lymphoma (NHL) [including DLBCL and FL] or in phase 2 or 3 development for previously untreated DLBCL, while polatuzumab vedotin monotherapy has been in phase 1 development for relapsed/refractory B-cell NHL in Japan. This article summarizes the milestones in the development of polatuzumab vedotin leading to this first approval for its use in combination with bendamustine plus rituximab for relapsed/refractory DLBCL.
Polatuzumab Vedotin for Relapsed/Refractory Aggressive B-cell Lymphoma: A Multicenter Post-marketing Analysis. [2022]Polatuzumab vedotin is approved therapy in the United States for relapsed/refractory diffuse large B-cell lymphoma in combination with bendamustine and rituximab (Pola+BR). However, the safety and efficacy of Pola+BR outside of a clinical trial setting is unknown.