Trial Summary
What is the purpose of this trial?The purpose of this study is to determine how effective and safe the combination of glofitamab and obinutuzumab is in treating patients with Follicular Lymphoma (FL) and Marginal Zone Lymphoma (MZL) who have not received other treatments for their lymphoma.
The names of the study drugs involved in this study are:
* Glofitamab (a type of immunotherapy)
* Obinutuzumab (a type of immunotherapy)
Is the drug Glofitamab and Obinutuzumab a promising treatment for Non-Hodgkin's Lymphoma?Yes, the drug combination of Glofitamab and Obinutuzumab is promising for treating Non-Hodgkin's Lymphoma. Obinutuzumab has shown to improve survival rates in patients who did not respond to previous treatments, and it is being considered as a potential new standard for certain types of lymphoma. It has been approved for use in difficult-to-treat cases, indicating its effectiveness.34568
What data supports the idea that Glofitamab + Obinutuzumab for Non-Hodgkin's Lymphoma is an effective treatment?The available research shows that Obinutuzumab, when used with other drugs like bendamustine, has been effective in treating certain types of Non-Hodgkin's Lymphoma, especially in patients who did not respond to or relapsed after previous treatments. In studies, this combination led to longer periods without the disease getting worse and improved overall survival compared to using bendamustine alone. Obinutuzumab has shown better results than the current standard treatment, rituximab, in some cases. This suggests that Glofitamab + Obinutuzumab could be a promising option for treating Non-Hodgkin's Lymphoma.25678
What safety data is available for the treatment of Glofitamab and Obinutuzumab in Non-Hodgkin's Lymphoma?Glofitamab, a bispecific antibody, has been evaluated in a phase I trial for relapsed or refractory B-cell non-Hodgkin lymphoma, showing durable complete remissions with obinutuzumab pretreatment to reduce toxicity. Obinutuzumab, also known as Gazyva, has been studied in various trials, including the GAUDI study, which showed that infusion-related reactions were the most common adverse events, with neutropenia being the most common hematologic adverse event. The GADOLIN study demonstrated that obinutuzumab had a manageable tolerability profile, with mild to moderate infusion-related reactions and neutropenia as common adverse events. The GALLIUM study showed that obinutuzumab-based immunochemotherapy improved progression-free survival compared to rituximab-based therapy, with serious adverse events reported in 48.9% of patients, but no new safety signals were identified. Overall, both treatments have shown acceptable safety profiles in clinical trials.1691011
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop your current medications. However, if you are on systemic immunosuppressive therapy or corticosteroids over 10 mg daily, you may not be eligible. A short course of steroids is allowed if stopped at least 7 days before treatment.
Eligibility Criteria
Adults with Follicular Lymphoma or Marginal Zone Lymphoma who haven't had systemic therapy for these conditions. They should have adequate organ function, no urgent need for chemotherapy, and agree to use effective contraception. Excluded are those with recent major surgery, uncontrolled infections, certain heart conditions, severe allergies to monoclonal antibodies, autoimmune diseases without clearance, prior transplants or immunosuppressive therapy needs.Treatment Details
The trial is testing the effectiveness and safety of combining two immunotherapy drugs: Glofitamab and Obinutuzumab in treating patients with Follicular Lymphoma (FL) and Marginal Zone Lymphoma (MZL). It's aimed at those who haven't received previous treatments for their lymphoma.
2Treatment groups
Experimental Treatment
Group I: Obinutuzumab + Glofitamab for Marginal Zone LymphomaExperimental Treatment2 Interventions
Participants will undergo study procedures as outlined:
* Imaging scans (CT or PET) at screening and after cycles 3, 7, and 12 of treatment.
* Bone marrow biopsy at baseline.
* Cycle 1
* Days -21, -14, -7, 0 of 36 day cycle: Predetermined dose of Obinutuzumab.
* Days 1 and 8 of 36 day cycle: Predetermined dose of Glofitamab. (First dose will be administered in the hospital.)
* Cycles 2 - 12:
o Day 1 of 21 day cycle: Predetermined dose of Glofitamab.
* Bone marrow biopsy within 2 weeks of end of treatment.
* Imaging scans (CT or PET) at 12, 18, and 24 months after treatment initiation.
* Follow up visits up to 5 years after treatment completion.
Group II: Obinutuzumab + Glofitamab for Follicular LymphomaExperimental Treatment2 Interventions
Participants will undergo study procedures as outlined:
* Imaging scans (CT or PET) at screening and after cycles 3, 7, and 12 of treatment.
* Bone marrow biopsy at baseline.
* Cycle 1
* Days -21, -14, -7, 0 of 36 day cycle: Predetermined dose of Obinutuzumab.
* Days 1 and 8 of 36 day cycle: Predetermined dose of Glofitamab. (First dose will be administered in the hospital.)
* Cycles 2 - 12:
o Day 1 of 21 day cycle: Predetermined dose of Glofitamab.
* Bone marrow biopsy within 2 weeks of end of treatment.
* Imaging scans (CT or PET) at 12, 18, and 24 months after treatment initiation.
* Follow up visits up to 5 years after treatment completion.
Glofitamab is already approved in United States for the following indications:
🇺🇸 Approved in United States as COLUMVI for:
- Relapsed or refractory diffuse large B-cell lymphoma not otherwise specified (DLBCL), or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy
Find a clinic near you
Research locations nearbySelect from list below to view details:
Beth Israel Deaconess Medical CenterBoston, MA
Columbia University Irving Medical CenterNew York, NY
Dana-Farber Cancer InstituteBoston, MA
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Who is running the clinical trial?
Reid Merryman, MDLead Sponsor
Genentech, Inc.Industry Sponsor
References
Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). [2022]The safety and activity of obinutuzumab (GA101) plus chemotherapy in relapsed/refractory follicular lymphoma was explored in 56 patients. Participants received obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP; every 3 weeks for 6 to 8 cycles) or obinutuzumab plus fludarabine and cyclophosphamide (G-FC; every 4 weeks for 4 to 6 cycles). Patients were randomly assigned to either obinutuzumab 1600 mg on days 1 and 8 of cycle 1 followed by 800 mg on day 1 of subsequent cycles or 400 mg for all doses. Treatment responders were eligible for obinutuzumab maintenance every 3 months for up to 2 years. Grade 1/2 infusion-related reactions (IRRs) were the most common treatment-related adverse event (AE) (all grades: G-CHOP, 68%; G-FC, 82%). Grade 3/4 IRRs were rare (7%) and restricted to the first infusion. All patients received the planned obinutuzumab dose. Neutropenia was the most common treatment-related hematologic AE for G-CHOP (43%) and G-FC (50%). At induction end, 96% (27/28) of patients receiving G-CHOP (complete response [CR], 39% [11/28]) and 93% (26/28) receiving G-FC (CR, 50% [14 of 28]) achieved responses. G-CHOP and G-FC had an acceptable safety profile with no new or unexpected AEs, but G-FC was associated with more AEs than G-CHOP. Obinutuzumab plus chemotherapy resulted in 93% to 96% response rates, supporting phase 3 investigation. This trial was registered at www.clinicaltrials.gov as #NCT00825149.
Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma. [2021]Obinutuzumab (GA101) is a novel glycoengineered type II CD20 antibody in development for non-Hodgkin lymphoma. We compared the anti-tumor activity of obinutuzumab and rituximab in preclinical studies using subcutaneous Z138 and WSU-DLCL2 xenograft mouse models. Obinutuzumab and rituximab were assessed alone and in combination with bendamustine, fludarabine, chlorambucil, doxorubicin and cyclophosphamide/vincristine. Owing to strong single-agent efficacy in these models, suboptimal doses of obinutuzumab were applied to demonstrate a combination effect. Obinutuzumab plus bendamustine achieved superior tumor growth inhibition versus rituximab plus bendamustine and showed a statistically significant effect versus the respective single treatments. Combinations of obinutuzumab with fludarabine, chlorambucil or cyclophosphamide/vincristine demonstrated significantly superior activity to rituximab-based treatment. Obinutuzumab monotherapy was at least as effective as rituximab plus chemotherapy in vivo, and obinutuzumab plus chemotherapy was superior to the respective monotherapies. These data support further clinical investigation of obinutuzumab plus chemotherapy.
Obinutuzumab: first global approval. [2021]Obinutuzumab (Gazyva™) is an intravenously administered, humanized and glycoengineered, type II anti-CD20 monoclonal antibody for the treatment of B-cell malignancies. It is approved in the US for use in combination with chlorambucil for the first-line treatment of chronic lymphocytic leukaemia (CLL), and has been filed for approval in the EU in this indication. The antibody is based on GlycArt Biotechnology's (later Roche Glycart AG) proprietary GlycoMAb® technology, which uses glycoengineered antibodies that specifically increase antibody-dependent cellular cytotoxicity and thereby increase immune-mediated target cell death. Obinutuzumab is a type II anti-CD20 antibody that induces enhanced direct cell death. The monoclonal antibody is in worldwide phase III development with Roche and its subsidiaries, Genentech and Chugai Pharmaceutical, as well as Biogen Idec, for diffuse large B-cell lymphoma and non-Hodgkin's lymphoma generally, and is also in phase III development in countries outside of the US and EU for CLL.
Obinutuzumab for the treatment of indolent lymphoma. [2018]Obinutuzumab is a humanized, type II anti-CD20 monoclonal antibody designed for strong induction of direct cell death and antibody-dependent cell-mediated cytotoxicity. The Phase III GADOLIN trial tested the clinical efficacy of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy in rituximab-refractory indolent non-Hodgkin lymphoma versus treatment with bendamustine alone. It demonstrated significantly longer progression-free survival for the obinutuzumab-containing regimen in this difficult to treat patient group. Based on the results of this trial, US FDA approval was most recently granted for obinutuzumab in the treatment of follicular lymphoma that has relapsed after or was refractory to a rituximab-containing regimen. This article summarizes the available data on chemistry, pharmacokinetics, clinical efficacy and safety of obinutuzumab in the treatment of indolent non-Hodgkin lymphoma.
Obinutuzumab in follicular lymphoma. [2017]The CD20 marker continues to be exploited as a therapeutic target for non-Hodgkin's lymphoma. Obinutuzumab is part of a new generation of anti-CD20 monoclonal antibodies, which are synthesized using molecular engineering technology, resulting in novel target epitopes and unprecedented optimization of antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Rituximab is the current gold standard for anti-CD20 therapy, yet despite outstanding results published over the past decade, many patients continue to relapse after anti-CD20 regimens. Obinutuzumab is slowly positioning itself in the treatment of CD20+ B-cell neoplasms. On the basis of favorable results from the phase III GADOLIN trial, obinutuzumab was recently approved by the U.S. Food and Drug Administration in combination with bendamustine followed by obinutuzumab maintenance, for the treatment of follicular lymphoma (FL) patients who relapsed or are refractory to a rituximab-containing regimen. Additional phase III trials are underway to test obinutuzumab as a first-line anti-CD20 agent in FL with good preliminary results (GALLIUM trial); thus, it is likely that obinutuzumab will soon achieve a first-line indication. It is plausible that obinutuzumab will replace rituximab as the gold standard for chemoimmunotherapy in FL, although some safety concerns still need to be resolved. This review will address the preclinical pharmacology and the main aspects of the clinical development of obinutuzumab for the treatment of FL.
Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma. [2018]Obinutuzumab (Gazyva®, Gazyvaro®) is a recombinant, monoclonal, humanized and glycoengineered, type II, anti-CD20, IgG1 antibody. It has recently been granted an additional indication for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen. In the primary analysis of the large, phase III GADOLIN study, induction therapy with obinutuzumab plus bendamustine followed by obinutuzumab maintenance prolonged progression-free survival (PFS) to a statistically significant extent relative to induction with bendamustine monotherapy in patients with indolent non-Hodgkin's lymphoma (iNHL). The improvement in PFS was largely driven by the subgroup of patients with follicular lymphoma, who also had prolonged overall survival (OS) in a planned updated analysis. Obinutuzumab had a generally manageable tolerability profile in these patients; mild to moderate infusion-related reactions (IRRs) were the most common treatment-emergent adverse events (AEs) and neutropenia the most common grade 3 or 4 treatment-related AEs. Although additional studies and longer-term data are needed to further assess treatment benefits with obinutuzumab, current evidence indicates that obinutuzumab is a useful treatment option for patients with rituximab-refractory or -relapsed follicular lymphoma.
Cost-effectiveness of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy for the treatment of follicular lymphoma patients who relapse after or are refractory to a rituximab-containing regimen in the US. [2019]Obinutuzumab (GA101, G) was approved in February 2016 by the US Food and Drug Administration to treat follicular lymphoma (FL) patients who relapsed after, or are refractory to (R/R), a rituximab-containing regimen (R/R-rituximab). In the GADOLIN trial, R/R-rituximab patients who received G plus bendamustine (B) followed by G-monotherapy (G + B) for up to 2 years had significantly improved progression-free survival and overall survival compared to patients receiving B-monotherapy. This study estimated the cost-effectiveness of G + B vs B-monotherapy for R/R-rituximab FL patients from a US payer perspective.
Cost-effectiveness analysis of treatment regimens with obinutuzumab plus chemotherapy in Japan for untreated follicular lymphoma patients. [2021]Obinutuzumab (GA101; G) is a new treatment for follicular lymphoma (FL) that is anticipated to have greater efficacy than the current treatment, rituximab (R). The aim of this study was to evaluate the cost-effectiveness of G plus chemotherapy (G + Chemo) against that of R plus chemotherapy (R + Chemo) for patients in Japan with previously untreated FL.
Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. [2023]Label="PURPOSE">Glofitamab is a T-cell-engaging bispecific antibody possessing a novel 2:1 structure with bivalency for CD20 on B cells and monovalency for CD3 on T cells. This phase I study evaluated glofitamab in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). Data for single-agent glofitamab, with obinutuzumab pretreatment (Gpt) to reduce toxicity, are presented.
Glofitamab: First Approval. [2023]Glofitamab (Columvi®) is a CD20 × CD3 T-cell-engaging bispecific monoclonal antibody being developed by Roche for the treatment of B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma (DLBCL). Glofitamab received its first approval (with conditions) on 25 March 2023, in Canada, for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, DLBCL arising from follicular lymphoma, or primary mediastinal B-cell lymphoma, who have received two or more lines of systemic therapy and are ineligible to receive or cannot receive CAR T-cell therapy or have previously received CAR T-cell therapy. Glofitamab is also under regulatory review for relapsed or refractory DLBCL in the EU and USA and in April 2023 received a positive opinion recommending the granting of a conditional marketing authorization in the EU. Clinical development of glofitamab, as a monotherapy and in combination with other agents for the treatment of non-Hodgkin lymphomas, is continuing worldwide. This article summarizes the milestones in the development of glofitamab leading to this first approval for relapsed or refractory DLBCL.
Obinutuzumab Versus Rituximab Immunochemotherapy in Previously Untreated iNHL: Final Results From the GALLIUM Study. [2023]The phase III GALLIUM trial assessed the safety and efficacy of obinutuzumab-based versus rituximab-based immunochemotherapy in patients with previously untreated follicular lymphoma (FL) or marginal zone lymphoma (MZL). At the primary analysis, the trial met its primary end point, demonstrating improvement in investigator-assessed progression-free survival (PFS) with obinutuzumab-based versus rituximab-based immunochemotherapy in patients with FL. We report the results of the final analysis in the FL population, with an additional exploratory analysis in the MZL subgroup. Overall, 1202 patients with FL were randomized 1:1 to obinutuzumab- or rituximab-based immunochemotherapy followed by maintenance with the same antibody for up to 2 years. After a median 7.9 (range, 0.0-9.8) years of follow-up, PFS remained improved with obinutuzumab- versus rituximab-based immunochemotherapy, with 7-year PFS rates of 63.4% versus 55.7% (P = 0.006). Time-to-next antilymphoma treatment was also improved (74.1% versus 65.4% of patients had not started their next antilymphoma treatment at 7 y; P = 0.001). Overall survival was similar between the arms (88.5% versus 87.2%; P = 0.36). Irrespective of the treatment received, PFS and OS were higher in patients with a complete molecular response (CMR) versus those with no CMR (P < 0.001). Serious adverse events were reported in 48.9% and 43.4% of patients in the obinutuzumab and rituximab arms, respectively; there was no difference in the rate of fatal adverse events (4.4% and 4.5%, respectively). No new safety signals were reported. These data demonstrate the long-term benefit of obinutuzumab-based immunochemotherapy and confirm its role as a standard-of-care for the first-line treatment of advanced-stage FL, taking into account patient characteristics and safety considerations.