Genentech Releases Positive Data from Broad Blood Cancer Portfolio

Genentech released new long-term follow-up results and sub analyses from clinical trials of its approved therapies at the European Hematology Association 2022 Congress in Vienna.

The data included 5-year results from a phase 3 CLL14 study of fixed-duration venetoclax (Venclexta) with obinutuzumab (Gazyva) in previously untreated chronic lymphocytic leukemia (CLL); the final analysis of the phase 3 GALLIUM study of obinutuzumab plus chemotherapy in individuals with previously untreated advanced-stage follicular lymphoma (FL); and subanalyses from the phase 3 POLARIX study of polatuzumab vedotin (Polivy) in combination with rituximab (Rituxan) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) in individuals with previously untreated diffuse large B-cell lymphoma (DLBCL).

In the phase 3 CLL14 study, venetoclax plus obinutuzumab continued to be an effective fixed-duration and chemotherapy-free option for individuals with CLL and coexisting conditions at a median of 65.4 months.

The estimated investigators assessed progression free survival (PFS) rate at the follow-up was 62.6% with the combination and 27% with obinutuzumab plus chlorambucil. The estimated overall survival (OS) rates were 81.9% and 77%, respectively.

Additionally, this analysis showed that 72.1% of individuals on the combination did not require another treatment for CLL in the 5 years following treatment. There were also no new safety signals observed.

In an 8-year follow-up of the phase 3 GALLIUM study, investigators saw a meaningful improvement of PFS with obinutuzumab plus chemotherapy, confirming that it is a standard of care for first-line treatment.

The 7-year PFS showed significant improvement with obinutuzumab plus chemotherapy at 63.4% compared with rituximab plus chemotherapy at 55.7%. Additionally, 74.1% of individuals receiving obinutuzumab plus chemotherapy had not started new anti-lymphoma therapies compared with 65.4% of those on rituximab plus chemotherapy.

Furthermore, the incidence of serious adverse events (AEs) was 48.9% with obinutuzumab plus chemotherapy and 43.4% with rituximab plus chemotherapy.

In the phase 3 POLARIX study, the results showed a significant improvement in PFS with polatuzumab vedotin plus R-CHP compared with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), reducing the risk of death, disease progression, or relapse by 36%. The safety profile was generally comparable for both combinations.

Additionally, the company announced the presentation of data on investigational medicines from its broad blood cancer portfolio at the conference, which will include data from its investigational T-cell engaging bispecific antibody development programs.

These data will include mosunetuzumab and glofitamab in individuals receiving later lines of therapy for non-Hodgkin lymphoma, as well as cevostamab and RG6234 in relapsed or refractory (R/R) multiple myeloma (MM).

In the phase 2 NP30179 expansion study, investigators found that fixed duration of glofitamab induced high and durable complete response (CR) rates in individuals with heavily pre-treated and highly refractory DLBCL.

Additionally, 39.4% of individuals achieved a CR, and half of them achieved an OR. Cytokine release syndrome (CRS) was the most common AE, occurring in 63% of individuals.

An exploratory subgroup analysis showed that mosunetuzumab could be an efficacious and tolerable option in individuals who had R/R FL and had received 2 or more prior therapies. Individuals aged 65 years or older achieved a higher objective response rate of 87% compared with those younger at 77%.

Lower rates of CRS and serious AEs were observed in individuals aged 65 years or older at 37% compared with those younger at 52%.

Additional data from the G029781 study showed that retreatment with mosunetuzumab in individuals who received a CR but whose disease subsequently progressed was effective and the safety of retreatment was consistent with the initial treatment.

Finally, Genentech will be presenting data at the conference on cevostamab, which is being evaluated as a monotherapy and in combination with other medications for those with R/R MM and RG6234, which is being studied in a phase 1 trial in individuals with R/R MM.

The clinical activity and safety profiles observed with these molecules are encouraging and support further exploration, according to the company.

Reference

Genentech announces positive data from broad blood cancer portfolio at European hematology association annual meeting. Genentech. News release. June 9, 2022. Accessed June 21, 2022. https://www.gene.com/media/press-releases/14956/2022-06-09/genentech-announces-positive-data-from-b