Post-CAR T-cell Therapy Drug Combo for Non-Hodgkin's Lymphoma
Palo Alto (17 mi)Overseen byBrian T Hess
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: SWOG Cancer Research Network
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing two treatments, mosunetuzumab and polatuzumab vedotin, for patients with certain types of lymphoma that have come back or don't respond to other treatments. These treatments aim to stop cancer cells from growing or kill them directly. The goal is to see if these treatments can better control or shrink the cancer compared to not using them.
What data supports the idea that Post-CAR T-cell Therapy Drug Combo for Non-Hodgkin's Lymphoma is an effective treatment?The available research shows that the combination of mosunetuzumab and polatuzumab vedotin is effective for treating relapsed or refractory aggressive large B-cell lymphoma. In a study, 59.2% of patients responded to the treatment, and 45.9% achieved complete remission. The median time patients lived without the disease getting worse was 11.4 months, and the median overall survival was 23.3 months. This suggests that the drug combo is effective, especially for patients who cannot undergo a transplant.14578
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot receive polatuzumab vedotin or mosunetuzumab as part of bridging therapy before the trial. It's best to discuss your current medications with the trial team to ensure eligibility.
Is the drug used in the trial 'Post-CAR T-cell Therapy Drug Combo for Non-Hodgkin's Lymphoma' a promising treatment?Yes, the drug polatuzumab vedotin, used in combination with other treatments, shows promise for patients with large B-cell lymphoma, especially those who have relapsed after CAR T-cell therapy. It has been shown to help some patients achieve remission and has been approved for treating certain types of lymphoma.12568
What safety data exists for the drug combination used after CAR T-cell therapy in Non-Hodgkin's Lymphoma?The combination of mosunetuzumab and polatuzumab vedotin has been evaluated in a phase 1b/2 trial for relapsed/refractory large B-cell lymphoma. The most common grade 3 or higher adverse events were neutropenia (25%) and fatigue (6.7%). Any-grade cytokine release syndrome occurred in 16.7% of patients, indicating a favorable safety profile. Polatuzumab vedotin has a low incidence of anti-drug antibodies, suggesting a low immunogenicity risk. In a retrospective study of polatuzumab vedotin after CAR T-cell therapy, 44% of patients responded to treatment, but 81% experienced disease progression or death, with a median progression-free survival of 10 weeks.13578
Eligibility Criteria
This trial is for adults with certain types of lymphoma (like diffuse large B-cell or follicular grade IIIb) that's come back or isn't responding to treatment. They should be set for CAR T-cell therapy, have a decent performance score, and functioning major organs. People can't join if they've had recent heart issues, used specific drugs as 'bridging' therapy, or if their CAR T-cells aren't FDA-approved.Treatment Details
The study tests mosunetuzumab and polatuzumab vedotin in patients who've had chemotherapy followed by CAR T-cell therapy. It aims to see if these drugs help control the cancer better post-CAR T-cell treatment compared to not using them.
5Treatment groups
Experimental Treatment
Active Control
Group I: Step II Arm III (polatuzumab vedotin, mosunetuzumab)Experimental Treatment5 Interventions
Patients receive polatuzumab vedotin IV and mosunetuzumab IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.
Group II: Step II Arm II (polatuzumab vedotin)Experimental Treatment4 Interventions
Patients receive polatuzumab vedotin IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.
Group III: Step II Arm I (mosunetuzumab)Experimental Treatment4 Interventions
Patients receive mosunetuzumab IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.
Group IV: Step I (lymphodepleting chemotherapy)Experimental Treatment6 Interventions
Patients receive lymphodepleting chemotherapy consisting of fludarabine IV and cyclophosphamide IV on study. Patients then receive tisagenlecleucel IV, axicabtagene ciloleucel IV, or lisocabtagene maraleucel IV on study.
Group V: Step II Arm IV (observation)Active Control4 Interventions
Patients undergo observation on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study. Patients with subsequent progression within 12 months of CAR T-cell therapy may crossover to Arm III.
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of Arkansas for Medical SciencesLittle Rock, AR
Geisinger Medical CenterDanville, PA
Weisberg Cancer Treatment CenterFarmington Hills, MI
Trinity Health Muskegon HospitalMuskegon, MI
More Trial Locations
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Who is running the clinical trial?
SWOG Cancer Research NetworkLead Sponsor
Southwest Oncology GroupLead Sponsor
Genentech, Inc.Industry Sponsor
National Cancer Institute (NCI)Collaborator
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.
Polatuzumab Vedotin Approved for DLBCL. [2020]The antibody-drug conjugate polatuzumab vedotin has been approved to treat relapsed or refractory diffuse large B-cell lymphoma. The drug recognizes the CD79b protein on B cells and kills them with a molecule that prevents tubulin polymerization.
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.
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.
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.
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.
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 .