– Results to be presented for the first time show mosunetuzumab induces high and durable complete response rates in people with follicular lymphoma who have received two or more prior therapies –

– New efficacy data from Genentech’s portfolio of cancer immunotherapies demonstrate potential of bispecific antibodies to expand upon current treatment options across several blood cancers –

SOUTH SAN FRANCISCO, CA, USA I December 11, 2021 I Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that new pivotal data on its CD20xCD3 T-cell engaging bispecific antibody, mosunetuzumab, will be presented for the first time at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition from December 11-14, 2021.

Emerging data continue to show the promising benefit-risk profile of mosunetuzumab in relapsed or refractory (R/R) follicular lymphoma (FL), a slow-growing, or indolent, form of non-Hodgkin’s lymphoma (NHL). Pivotal results from the Phase I/II GO29781 study demonstrated that mosunetuzumab induces durable complete responses lasting at least 18 months in heavily pretreated patients with R/R FL who have received two or more prior therapies, with a 60.0% complete response (CR) rate and a median progression-free survival of 17.9 months (95% CI: 10.1-not evaluable). Median duration of response was 22.8 months among responders (95% CI: 9.7-not evaluable). The most common adverse event (AE) was cytokine release syndrome (CRS), which was generally low grade (mainly Grade 1-2).

“Despite initial successful treatment, many people with follicular lymphoma often experience relapse. Mosunetuzumab could potentially become a highly efficacious treatment option that can be administered without the need for cell collection or genetic engineering,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “With mosunetuzumab, we also aim to offer a therapy that can be administered in the outpatient setting to people with this devastating blood cancer.”

Genentech plans to submit the new data to the U.S. Food and Drug Administration in the near future for approval consideration. If approved, mosunetuzumab has the potential to be a first-in-class CD20xCD3 T-cell engaging bispecific antibody in NHL. Roche recently submitted the initial marketing authorization application for mosunetuzumab to the European Medicines Agency, with the hope to bring this drug as soon as possible to people with NHL.

Additionally, as part of Genentech’s broad pipeline of hematology immunotherapies and application of novel combinations, key data for the bispecific antibodies mosunetuzumab, glofitamab and cevostamab are being presented, including:

  • Initial results from the Phase Ib CO41942 study of mosunetuzumab in combination with lenalidomide in people with R/R FL who have received at least one prior line of therapy demonstrated encouraging preliminary efficacy and a tolerable safety profile.
  • Data from the Phase Ib/II GO40516 study evaluating mosunetuzumab in combination with Polivy® (polatuzumab vedotin-piiq) showed promising efficacy and favorable safety in heavily pretreated patients with aggressive R/R NHL with an objective response rate (ORR) of 65.0% and a CR rate of 48.3%. CRS occurred in 18% of patients, and all events occurred in Cycle 1 and were Grade 1-2.
  • A Phase I/Ib NP30179 dose-escalation study evaluating glofitamab as a monotherapy and in combination with Gazyva® (obinutuzumab) following pretreatment with Gazyva in patients with R/R B-cell NHL showed promising activity in both R/R FL and R/R mantle cell lymphoma (MCL), an uncommon but aggressive form of lymphoma with poor prognosis for those who progress.
    • Preliminary results in heavily pretreated patients with R/R FL showed high response rates across all treatment groups, including high-risk subgroups, with an ORR of 81.0% for the glofitamab monotherapy group and an ORR of 100% for the glofitamab plus Gazyva combination therapy group. For patients with R/R MCL treated with glofitamab monotherapy following Gazyva pretreatment, the ORR was 81.0%. Across both studies, the most common AE was CRS, with the majority of events being low grade (Grade 1-2).
  • Results of the Phase Ib/II NP39488 study of glofitamab in combination with Polivy demonstrated encouraging preliminary efficacy and a tolerable safety profile in people with difficult-to-treat R/R diffuse large B-cell lymphoma. With a median follow up of 3.2 months (95% CI: 1.4-3.5), an ORR of 73.0% was observed with a 51.5% CR rate, with patients showing durable responses at ≥6 months. No Grade 3 or higher CRS events were observed, and the safety profile of the combination was consistent with that of the individual medicines.
  • Data from the Phase I GO39775 dose-escalation and expansion study investigating cevostamab in heavily pretreated patients with R/R multiple myeloma (MM) showed the first-of-its kind FcRH5xCD3 bispecific antibody induced clinically meaningful, target dose-dependent increases in ORR without an increase in the rate of CRS, with an ORR of 54.5% in the 160 mg dose group. Results from double step-up dosing suggest this approach could help mitigate CRS and potentially improve the safety profile compared to single step-up dosing.

Our investigational cancer immunotherapies, mosunetuzumab and glofitamab, are T-cell engaging bispecific antibodies designed to engage with CD3 on the T cell and CD20 on the tumor cell, bringing them close in proximity and enabling the T cell to eliminate the tumor cell. Although these bispecific antibodies have similar modes of action, they differ in their structure and clinical profiles. Cevostamab, another investigational T-cell engaging bispecific antibody, is designed to target FcRH5 on myeloma cells and CD3 on T cells and is currently being evaluated in people living with R/R MM.

Genentech’s broad and comprehensive clinical development program will continue to evaluate mosunetuzumab, glofitamab and cevostamab as monotherapies and in combination with other established and/or novel therapies for malignant hematological conditions with the goal of providing treatment solutions tailored to the patient journey for each disease.

Keep up to date with ASH 2021 news and updates by using the hashtag #ASH21 and follow Genentech on Twitter via @Genentech and on LinkedIn.

About Genentech’s Investigational Bispecifics in Hematology

Genentech is currently developing two T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, 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. Mosunetuzumab and glofitamab differ in their structures, and both are being developed by Genentech as part of our ongoing strategy to explore multiple bispecific formats, to identify those that maximize potential clinical benefits for patients. Mosunetuzumab has a structure similar to that of a natural human antibody in that it has two ‘Fab’ regions, but is different from naturally-occurring antibodies in that one ‘Fab’ region targets CD20 and the other ‘Fab’ region targets CD3. 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 that bind to CD20 and one ‘Fab’ region that binds to CD3. The clinical development programs for mosunetuzumab and glofitamab include ongoing investigations of these molecules as monotherapies and in combination with other medicines for the treatment of people with CD20-positive B cell (non-Hodgkin’s lymphomas), including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).

About Cevostamab (FcRH5xCD3 Bispecific Antibody)

Cevostamab (BFCR4350A) is an FcRH5xCD3 T-cell engaging bispecific antibody designed to target FcRH5 on myeloma cells and CD3 on T cells. FcRH5 is a unique and differentiated target, expressed on nearly all myeloma cells. Cevostamab has a structure similar to that of a natural human antibody in that it has two ‘Fab’ regions, but is different from naturally-occurring antibodies in that one ‘Fab’ region targets FcRH5 and the other ‘Fab’ region targets CD3. This dual targeting activates and re-directs a patient’s existing T cells to engage and eliminate target FcRH5-expressing myeloma cells by releasing cytotoxic proteins into the myeloma cells.

About the GO29781 Study

The GO29781 study [NCT02500407] is a Phase I/II, multicenter, open-label, dose-escalation study evaluating the safety and pharmacokinetics of mosunetuzumab in people with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Outcome measures include complete response rate (best response) by independent review facility (primary endpoint), objective response rate, duration of response, progression-free survival, and safety and tolerability (secondary endpoints).

Polivy U.S. Indication

Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat diffuse large B-cell lymphoma in adults who have progressed after at least two prior therapies.

The accelerated approval of Polivy is based on a type of response rate. There are ongoing studies to confirm the clinical benefit of Polivy.

Please visit http://www.Polivy.com for the full Prescribing Information for additional Important Safety Information.

Gazyva U.S. Indication

Gazyva is a prescription medicine used with the chemotherapy drug, bendamustine, followed by Gazyva alone for follicular lymphoma (FL) in adults who did not respond to a rituximab-containing regimen, or whose FL returned after such treatment.

Please visit http://www.Gazyva.com for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.

About Genentech in Hematology

For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit http://www.gene.com/hematology.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

SOURCE: Genentech