Mosunetuzumab + Polatuzumab Vedotin for Follicular Lymphoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Washington University School of Medicine
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This phase II clinical trial studies the combination of mosunetuzumab and polatuzumab vedotin in order to see how well it works in patients with untreated follicular lymphoma. Mosunetuzumab is an antibody that has been engineered to attach to two target cells in the immune system: T cells that normally perform tasks like killing virus-infected cells, and cancerous B cells. Mosunetuzumab has been designed to direct these T cells to kill the cancerous B cells instead. Polatuzumab vedotin is an antibody-drug conjugate that attaches to certain cancerous B cells and then delivers a drug specifically to those cells.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have been on certain immunosuppressive medications within 2 weeks before starting the trial. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug Mosunetuzumab + Polatuzumab Vedotin for Follicular Lymphoma?
Polatuzumab vedotin has shown effectiveness in treating diffuse large B-cell lymphoma, a type of blood cancer, especially when combined with other drugs like rituximab. This suggests it might also be effective in treating similar conditions like follicular lymphoma.
12345Is the combination of Mosunetuzumab and Polatuzumab Vedotin safe for humans?
The combination of Mosunetuzumab and Polatuzumab Vedotin has been studied in patients with relapsed or refractory large B cell lymphoma, showing a favorable safety profile. Common side effects included neutropenia (low white blood cell count) and fatigue, with some patients experiencing cytokine release syndrome (a reaction that can cause fever and low blood pressure).
15678What makes the drug combination of Mosunetuzumab and Polatuzumab Vedotin unique for treating follicular lymphoma?
The combination of Mosunetuzumab and Polatuzumab Vedotin is unique because it targets two different components of B-cells: Mosunetuzumab targets CD20, while Polatuzumab Vedotin targets CD79b. This dual targeting approach may enhance the effectiveness of treatment by attacking the cancer cells from multiple angles.
128910Eligibility Criteria
Adults diagnosed with untreated follicular lymphoma grades 1-3A, stages II-IV. Participants must have certain symptoms or tumor sizes, be in good physical condition (ECOG ≤2), and have adequate organ function. They should not have had prior treatments for this lymphoma or other recent immunotherapies, CNS diseases, severe allergies to monoclonal antibodies, active infections like hepatitis B/C or HIV, autoimmune diseases requiring treatment, or any serious medical conditions that could interfere with the trial.Inclusion Criteria
I have been diagnosed with a type of lymphoma that is not the most aggressive form.
Exclusion Criteria
Prior history of aggressive B cell lymphoma such as diffuse large B cell lymphoma or high-grade B cell lymphoma, Known history of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, Known history of macrophage activation syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH), Current or past history of CNS lymphoma, Any prior systemic therapy for follicular lymphoma, Treatment with radiotherapy within 2 weeks prior to the first dose of mosunetuzumab (otherwise one measurable lesion outside of the radiation field must remain), Treatment with any anti-CD20 monoclonal antibody within 4 weeks of Day 1 of Cycle 1, Current or recent history (within the last 6 months) of CNS disease, Treatment with systemic immunosuppressive medications, History of solid organ transplantation, History of allogeneic stem cell transplantation, Prior treatment with chimeric antigen receptor T cell therapy within 30 days before Day 1 of Cycle 1, History of severe allergic or anaphylactic reaction to humanized, chimeric, or murine monoclonal antibodies (mAbs), Known hypersensitivity to biopharmaceuticals produced in CHO cells or any component of the mosunetuzumab formulation, History of erythema multiforme, Grade ≥ 3 rash, or blistering following prior treatment with immunomodulatory derivatives, Known active bacterial, viral, fungal, or other infection, Known or suspected chronic active Epstein-Barr virus (EBV) infection, Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease, Active hepatitis B infection, Active hepatitis C infection, Known history of human immunodeficiency virus (HIV) positive status, History of progressive multifocal leukoencephalopathy (PML), Administration of a live, attenuated vaccine within 4 weeks before first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study, Other malignancy that could affect compliance with the protocol or interpretation of results, Active autoimmune disease requiring treatment, Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1 Day 1 or anticipation of a major surgical procedure during the course of the study, Pregnant or lactating or intending to become pregnant during the study, Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results.
Participant Groups
The trial is testing a combination of two drugs: Mosunetuzumab and Polatuzumab vedotin on patients who haven't been treated before for follicular lymphoma. Mosunetuzumab directs immune cells to attack cancerous cells while Polatuzumab delivers a drug directly to them.
1Treatment groups
Experimental Treatment
Group I: Mosunetuzumab and Polatuzumab VedotinExperimental Treatment2 Interventions
Patients receive CD3xCD20 bispecific antibody mosunetuzumab administered subcutaneously in combination with CD79b directed ADC polatuzumab vedotin administered intravenously. Mosunetuzumab and polatuzumab vedotin are given in combination for 6 cycles. Mosunetuzumab is given on Days 1, 8, and 15 of cycle 1 and then Day 1 thereafter, and polatuzumab vedotin is given on Day 1. After 6 cycles, patients continue on mosunetuzumab alone for 2 additional cycles. Patients undergo scans at the end of cycle 8, and if those scans show a complete response, patients will stop any further treatment and will enter follow-up. Patients with a partial response or stable disease on scans at the end of cycle 8 may receive up to 9 additional cycles of mosunetuzumab in the absence of disease progression or unacceptable toxicity. All cycles are planned to be 21 days.
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:
Washington University School of MedicineSaint Louis, MO
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Who is running the clinical trial?
Washington University School of MedicineLead Sponsor
Genentech, Inc.Industry Sponsor
Institute for Follicular LymphomaCollaborator
References
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.
United we stand: Double targeting of CD79B and CD20 in diffuse large B-cell lymphoma. [2023]Polatuzumab vedotin is antibody-drug conjugate (ADC) targeting CD79B approved for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma when given in combination with bendamustine and rituximab. The report by Kawasaki et al. provide hints on what might be happening in lymphoma cells exposed to polatuzumab vedotin and to rituximab and on potential mechanism of resistance to the ADC. Commentary on: Kawasaki et al. The molecular rationale for the combination of polatuzumab vedotin plus rituximab in diffuse large B-cell lymphoma. Br J Haematol 2022;199:245-255.
Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2021]Patients with transplantation-ineligible relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) fare poorly, with limited treatment options. The antibody-drug conjugate polatuzumab vedotin targets CD79b, a B-cell receptor component.
Polatuzumab vedotin: an investigational anti-CD79b antibody drug conjugate for the treatment of diffuse large B-cell lymphoma. [2022]New agents for managing B-cell non-Hodgkin lymphomas (NHLs) are needed, particularly for high-risk and relapsed or refractory patients. Antibody-drug conjugates (ADCs) provide targeted drug delivery to tumors with a broaden therapeutic index of cytotoxic agent, reducing their systemic toxicity while increasing intracellular concentrations. Polatuzumab vedotin, an anti-CD79b conjugated to the microtubule inhibitor monomethyl auristatin E (MMAE) raises particular interest.
Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. [2018]Patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) have an unfavourable prognosis with few treatment options. Polatuzumab vedotin is an antibody-drug conjugate containing an anti-CD79B monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the safety and clinical activity of polatuzumab vedotin in relapsed or refractory B-cell NHL and chronic lymphocytic leukaemia (CLL).
Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. [2023]Relapsed/refractory aggressive large B cell lymphoma (LBCL) remains an area of unmet need. Here we report the primary analysis of a phase 1b/2 trial of outpatient mosunetuzumab (a CD20xCD3 T-cell-engaging bispecific antibody) plus polatuzumab vedotin (an anti-CD79B antibody-drug conjugate) in relapsed/refractory LBCL. The phase 2 component is a single arm of an ongoing multi-arm trial. The primary endpoint during dose expansion was independent review committee (IRC)-assessed best overall response rate. Secondary endpoints included investigator-assessed overall response rate, complete response, duration of response, progression-free survival and overall survival. At data cutoff, 120 patients were enrolled (22 dose escalation, 98 dose expansion). The primary endpoint was met during dose expansion, with IRC-assessed best overall response rate and complete response rates of 59.2% (58/98; 95% confidence interval (CI): 48.8-69.0) and 45.9% (45/98; 95% CI: 35.8-56.3), respectively (median follow-up, 23.9 months). Median duration of complete was not reached (95% CI: 20.5-not estimable (NE)). Median progression-free survival was 11.4 months (95% CI: 6.2-18.7). Median overall survival was 23.3 months (95% CI: 14.8-NE). Across dose escalation and expansion, the most common grade 3 or higher adverse events were neutropenia (25.0%, 30/120) and fatigue (6.7%, 8/120). Any-grade cytokine release syndrome occurred in 16.7% of patients. These data demonstrate that mosunetuzumab plus polatuzumab vedotin has a favorable safety profile with highly durable responses suitable as second-line therapy in transplant-ineligible relapsed/refractory LBCL. ClinicalTrials.gov identifier: NCT03671018 .
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.
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.
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.
Evaluation and use of an anti-cynomolgus monkey CD79b surrogate antibody-drug conjugate to enable clinical development of polatuzumab vedotin. [2021]Polatuzumab vedotin is an antibody-drug conjugate (ADC) being developed for non-Hodgkin's lymphoma. It contains a humanized anti-CD79b IgG1 monoclonal antibody linked to monomethyl auristatin E (MMAE), an anti-mitotic agent. Polatuzumab vedotin binds to human CD79b only. Therefore, a surrogate ADC that binds to cynomolgus monkey CD79b was used to determine CD79b-mediated pharmacological effects in the monkey and to enable first-in-human clinical trials.