On June 12, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported updated data on one of its investigational CD20xCD3 T-cell engaging bispecific antibodies, glofitamab (formerly known as CD20-TCB), in people with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) (Press release, Hoffmann-La Roche, JUN 12, 2020, View Source [SID1234561027]). Updated results from the phase I dose-escalation NP30179 study [NCT03075696] of glofitamab, administered via intravenous infusion for a fixed-duration of up to 12 21-day cycles, showed durable complete responses (CRs) in heavily pre-treated patients who had received a median of three prior lines of therapy. These data feature in an oral presentation (abstract #S241) at the European Hematology Association (EHA) (Free EHA Whitepaper) 25th Annual Congress Virtual Edition, taking place from 11-14 June 2020.

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"Non-Hodgkin lymphomas such as diffuse large B-cell lymphoma may present considerable treatment challenges, especially cases involving multiple relapses," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "We’re encouraged by these early results which support the potential of glofitamab for patients who have failed multiple prior lines of therapy and need new treatment options urgently."

Updated efficacy data from the ≥0.6mg and ≥10mg cohorts showed high response rates across NHL subtypes.

In the ≥0.6mg cohorts, the investigator-assessed CR rate was 30.9% (38/123) for patients with aggressive NHL and the investigator-assessed overall response rate (ORR) was 45.5% (56/123). For patients with indolent NHL, the investigator-assessed CR rate was 52.2% (12/23) and the investigator-assessed ORR was 65.2% (15/23).
In the ≥10mg cohorts, the investigator-assessed CR rate was 34.1% (29/85) for patients with aggressive NHL and the investigator-assessed ORR was 49.4% (42/85). For patients with indolent NHL, the investigator-assessed CR rate was 50.0% (9/18) and the investigator-assessed ORR was 66.7% (12/18).
CRs also appeared durable. Of the patients achieving a CR in the ≥0.6mg cohorts, 72.7% (24/33) with aggressive NHL and 81.8% (9/11) with indolent NHL maintained their CR by the data cut-off date (17 April 2020). Median duration of CR was not reached in either group after a median follow-up of 10.2 months.
The safety profile of glofitamab was consistent with its mechanism of action. Common adverse events (AEs) occurring in over 15% of participants in the ≥0.6mg cohorts (n=156) were cytokine release syndrome (CRS; n=88, 56.4%), neutropenia (n=48, 30.8%), pyrexia (n=47, 30.1%), anaemia (n=35, 22.4%) and thrombocytopenia (n=26, 16.7%). The majority of CRS events were low grade (Grade 1-2), were associated with the first cycle, and were manageable.

A robust clinical development programme for glofitamab is ongoing, investigating the molecule alone and in combination with other Roche and non-Roche molecules. Combination regimens include studies with Polivy (polatuzumab vedotin), Tecentriq (atezolizumab), MabThera/Rituxan (rituximab) and Gazyva/Gazyvaro (obinutuzumab) in NHL and other blood cancers, across a variety of settings and tumour types, including earlier treatment lines, to identify where glofitamab may be able to provide benefit over current treatment options.

About glofitamab
Glofitamab is an investigational CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells. This dual targeting activates and redirects a patient’s existing T-cells to engage and eliminate target B-cells by releasing cytotoxic proteins into the B-cells. Glofitamab is based on a novel structural format which we call ‘2:1’, which refers to the structure of the antibody. It is engineered to have two ‘Fab’ regions which bind to CD20, and one ‘Fab’ region which binds to CD3. 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 CD20-positive B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma and follicular lymphoma, and other blood cancers.

About the NP30179 study
The NP30179 study [NCT03075696] is a phase I/Ib, multicentre, open-label, dose-escalation study, evaluating the efficacy, safety, tolerability and pharmacokinetics of glofitamab. In this study, glofitamab is assessed as a single agent and in combination with Gazyva/Gazyvaro (obinutuzumab), following pre-treatment with a one-time, fixed dose of Gazyva/Gazyvaro, in people with relapsed or refractory B-cell non-Hodgkin lymphoma. Outcome measures include overall response rate, complete response rate per Lugano 2014 criteria, maximum tolerated dose, and tolerability.

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 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, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes idasanutlin, a small molecule which inhibits the interaction of MDM2 with p53; T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, targeting both CD20 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.