If approved, glofitamab would be the first fixed-duration CD20xCD3 T-cell engaging bispecific antibody approved to treat the most aggressive type of non-Hodgkin lymphoma
Results from the pivotal phase I/II NP30179 study showed glofitamab induced durable response rates in people with heavily pre-treated large B-cell lymphoma, with 40% achieving a complete response
Glofitamab is part of Roche’s industry-leading portfolio of T-cell engaging bispecific antibodies, which also includes the newly FDA-approved first-in-class Lunsumio to treat follicular lymphoma
Basel, 6 January 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) and granted priority review for glofitamab, an investigational CD20xCD3 T-cell engaging bispecific antibody, for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. LBCL is an aggressive (fast-growing) type of non-Hodgkin lymphoma (NHL) and is one of the most prevalent types of blood cancer among adults in the U.S.1 The FDA is expected to make a decision on approval of this novel cancer immunotherapy by 1 July 2023. If approved, glofitamab would be the first fixed-duration, off-the-shelf CD20xCD3 T-cell engaging bispecific antibody available to treat people with an aggressive lymphoma who have previously received multiple courses of treatment.
“Unfortunately, people with relapsed or refractory large B-cell lymphoma have a poor prognosis and desperately need additional therapies that are immediately available at the time of relapse,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Even for patients whose cancer is rapidly progressing, glofitamab given for a fixed duration has shown impressive efficacy and long-term durability, with patients continuing to experience a complete remission after treatment has concluded.”
The BLA is based on positive data from the pivotal phase I/II NP30179 study, which included patients who had previously received multiple courses of therapy, with 85.1% of patients refractory to their most recent therapy and about one-third (33.1%) having received prior CAR T-cell therapy. Results showed that 40.0% of patients (n=62/155) achieved a complete response (CR; a disappearance of all signs of cancer), and 51.6% (n=80/155) achieved an objective response (OR; the combination of CR and partial response, a decrease in the amount of cancer in their body). The median follow-up time was 13.4 months. Among those who achieved a CR, 73.1% continued to experience a response at 12 months, while the median duration of CR was not reached. The median duration of response was 18.4 months.
An earlier cut-off of data from the phase I/II study showed that glofitamab given as a fixed-duration treatment resulted in early and durable complete remissions. In this analysis, presented at the 64th American Society of Hematology 2022 Annual Meeting and simultaneously published in the New England Journal of Medicine in December 2022, most patients who had achieved a CR at the end of treatment experienced durable responses. The median CR follow-up from the end of treatment was 11.5 months (95% confidence interval [CI]: 10.5-16.4). Twelve months after the end of treatment with glofitamab, 61% of patients (n=37/61) maintained a CR, 92.6% remained progression-free and only one patient (n=1/44) experienced disease progression.2,3
The most common adverse event was cytokine release syndrome (CRS), which was generally low grade (48.1% of patients had Grade 1 and 12.3% had Grade 2). Most CRS events were associated with initial administration of glofitamab (in cycle 1). The incidence of Grade 3 or higher CRS was 3.9%, with no Grade 5 events. Only one patient (n=1/155) discontinued glofitamab due to CRS.
The FDA will review the glofitamab BLA under the granted Fast Track Designation. Data from the phase I/II NP30179 study of glofitamab were submitted for review to the European Medicines Agency, and submissions to additional health authorities worldwide are ongoing.
Glofitamab is part of Roche’s industry-leading CD20xCD3 T-cell engaging bispecific antibody clinical programme, which is the broadest and most advanced in lymphoma. Roche’s portfolio also includes Lunsumio® (mosunetuzumab), which was granted accelerated approval by the FDA, and conditional marketing authorisation by the European Commission for the treatment of adults with R/R follicular lymphoma who have received at least two prior systemic therapies.
A robust clinical development programme for glofitamab is ongoing, including the phase III STARGLO trial, evaluating glofitamab in combination with gemcitabine and oxaliplatin (GemOx) versus rituximab in combination with GemOx in patients with second line plus diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant. Additional studies are ongoing to investigate the molecule as a monotherapy and in combination with other medicines for the treatment of patients with B-cell NHLs, including DLBCL, mantle cell lymphoma and other blood cancers.
About the NP30179 study
The NP30179 study [NCT03075696] is a phase I/II, multicentre, open-label, dose-escalation and expansion study evaluating the safety, efficacy and pharmacokinetics of glofitamab in people with relapsed or refractory diffuse large B-cell lymphoma. Outcome measures include complete response rate by an independent review committee (primary endpoint), overall response rate, duration of response, progression-free survival, safety, and tolerability (secondary endpoints).
About Large B-Cell Lymphoma
Large B-cell lymphoma (LBCL) is an aggressive (fast-growing) blood cancer and is one of the most prevalent blood cancers among adults.1 Diffuse large B-cell lymphoma (DLBCL), a subtype of LBCL, is the most common form of non-Hodgkin lymphoma (NHL) and accounts for almost a third of NHL diagnoses.4 While many patients are responsive to initial treatment, four out of ten are not cured with the current standard of care, and the majority of patients who require subsequent lines of therapy have poor outcomes.
About glofitamab
Glofitamab is an investigational CD20xCD3 T-cell-engaging bispecific antibody designed to target CD3 on the surface of T-cells and CD20 on the surface of B-cells. Glofitamab was designed with a novel 2:1 structural format. This T-cell-engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T-cells, a type of immune cell, and two regions that bind to CD20, a protein on B-cells, which can be healthy or malignant. This dual-targeting brings the T-cell in close proximity to the B-cell, activating the release of cancer cell-killing proteins from the T-cell. A robust clinical development programme for glofitamab is ongoing, investigating the molecule as a monotherapy and in combination with other medicines for the treatment of people with B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma and other blood cancers.
About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for more than 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab) and Lunsumio® (mosunetuzumab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies glofitamab, targeting both CD20 and CD3, and cevostamab, targeting both FcRH5 and CD3; Tecentriq® (atezolizumab), a monoclonal antibody designed to bind with PD-L1 and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.
About Roche
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.
Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.
Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the twelfth consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).
The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2020 employed more than 100,000 people worldwide. In 2020, Roche invested CHF 12.2 billion in R&D and posted sales of CHF 58.3 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan