Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that it is presenting new long-term follow-up results and subanalyses from clinical trials of its approved therapies, as well as data on investigational medicines from its broad blood cancer portfolio, at the European Hematology Association (EHA) 2022 Congress in Vienna. Data include five-year results from the phase III CLL14 study of fixed-duration Venclexta®/Venclyxto® (venetoclax) plus Gazyva®/Gazyvaro® (obinutuzumab) in previously untreated chronic lymphocytic leukaemia (CLL); the final analysis of the phase III GALLIUM study of Gazyva/Gazyvaro plus chemotherapy in people with previously untreated advanced-stage follicular lymphoma (FL); and subanalyses from the phase III POLARIX study of Polivy® (polatuzumab vedotin) in combination with MabThera®/Rituxan® (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Roche will also present data from its T-cell engaging bispecific antibody development programmes including Lunsumio® (mosunetuzumab) and glofitamab in patients receiving later lines of therapy for non-Hodgkin lymphoma (NHL) and investigational medicines cevostamab and RG6234 in relapsed or refractory (R/R) multiple myeloma (MM).
“Blood cancers remain challenging to treat at all stages, but by improving frontline treatment options we aim to increase the likelihood of meaningful clinical outcomes for these patients,” said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development. “With these new long-term data and other studies of fixed-duration therapies in our portfolio, we are working to lessen the treatment burdens associated with long-term cancer care.”
Improving clinical outcomes with effective frontline treatment options
Five-year results of phase III CLL14 study of Venclexta/Venclyxto plus Gazyva/Gazyvaro (Abstract #S148)
After a median of 65.4 months following treatment with Venclexta/Venclyxto plus Gazyva/Gazyvaro, results confirm the combination continues to be an effective fixed-duration and chemotherapy-free option for patients with previously untreated CLL and coexisting conditions. The estimated investigator-assessed progression-free survival (PFS) rate at this follow-up was 62.6% with Venclexta/Venclyxto plus Gazyva/Gazyvaro and 27.0% with Gazyva/Gazyvaro plus chlorambucil, and the estimated overall survival (OS) rate was 81.9% versus 77.0% (HR 0.72; 95% CI: 0.48-1.09; p=0.12). In addition, the analysis found that 72.1% of patients in the Venclexta/Venclyxto plus Gazyva/Gazyvaro arm did not require another treatment for CLL in the five years following initial treatment (HR 0.42; 95% CI: 0.31-0.57; p<0.0001). No new safety signals were observed.[1] The CLL14 study is being conducted in cooperation with the German CLL Study Group, headed by Michael Hallek, M.D., University of Cologne.
Final analysis of phase III GALLIUM study of Gazyva/Gazyvaro (Abstract #S206)
After eight years of follow-up in people with previously untreated FL, a meaningful improvement in PFS was maintained with Gazyva/Gazyvaro plus chemotherapy, confirming its role as a standard of care for first-line treatment. Seven-year investigator-assessed PFS was significantly improved with Gazyva/Gazyvaro plus chemotherapy (63.4%) compared with MabThera/Rituxan plus chemotherapy (55.7%; HR 0.77; 95% CI: 0.64-0.93; p=0.006). This translated into a longer time to next anti-lymphoma treatment. At seven years, 74.1% of patients receiving Gazyva/Gazyvaro plus chemotherapy had not started new anti-lymphoma therapy compared to 65.4% receiving MabThera/Rituxan plus chemotherapy (HR 0.71; 95% CI: 0.58–0.87; p=0.001). The incidence of serious adverse events was 48.9% with Gazyva/Gazyvaro plus chemotherapy and 43.4% with MabThera/Rituxan plus chemotherapy.[2]
Subgroup analyses of pivotal phase III POLARIX study (Abstract #P1192)
Exploratory subgroup analyses of the phase III POLARIX study of Polivy with R-CHP compared to the current standard of care, MabThera/Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), in people with previously untreated DLBCL further support the potential for Polivy to transform the standard of care for people with this aggressive type of lymphoma. One of the datasets being presented is an analysis of study participants from Asia (China, Hong Kong, Japan, South Korea and Taiwan). Among this subgroup, results showed a significant improvement in PFS with Polivy plus R-CHP versus R-CHOP, reducing the risk of disease progression, relapse or death by 36% (HR 0.64; 95% CI: 0.40-1.03). The safety profile was generally comparable for both regimens.[3]
Based on the positive POLARIX results from the overall study population, the European Commission (EC) approved Polivy plus R-CHP in May 2022 for the treatment of adult patients with previously untreated DLBCL.
Providing novel bispecific antibodies for patients receiving later lines of therapy in lymphoma and beyond
Pivotal data from phase II NP30179 expansion study of glofitamab (Abstract #S220)
The pivotal phase II NP30179 expansion study included patients with heavily pre-treated and highly refractory DLBCL and showed fixed-duration glofitamab, an investigational CD20xCD3 T-cell engaging bispecific antibody, induced high and durable complete response (CR) rates. After a median follow-up of 12.6 months, 39.4% of patients (n=61/155) achieved a CR (primary efficacy endpoint) and half of them (51.6%; n=80/155) achieved an overall response (the percentage of patients with a partial or CR; secondary efficacy endpoint), as assessed by an independent review committee. Cytokine release syndrome (CRS) was the most common adverse event, occurring in 63.0% of patients.[4] These data were recently presented at the American Society of Clinical Oncology 2022 Annual Meeting and have been submitted for approval to the European Medicines Agency (EMA). Submissions to additional health authorities worldwide, including the U.S. Food and Drug Administration (FDA), are planned this year.
Subgroup analysis and Lunsumio retreatment from pivotal phase II GO29781 study (Abstracts #P1126 and #P1124)
An exploratory subgroup analysis showed Lunsumio could be an efficacious and tolerable option in patients aged <65 and ≥65 years who had R/R FL and had received two or more prior therapies. Patients ≥65 years old achieved a higher objective response rate (ORR) than those <65 years old (87.0% vs 77.0%, respectively). Lower rates of CRS and serious adverse events were observed in patients ≥65 years old (37%) compared to those <65 years old (52%).[5] Additional data from the GO29781 study showed that retreatment with Lunsumio in patients who achieved a CR but whose disease subsequently progressed was effective and the safety of retreatment was consistent with initial treatment.[6]
The EC recently approved Lunsumio for the treatment of people with R/R FL who have received at least two prior systemic therapies.
The data being presented at EHA, as well as phase III studies currently underway, will expand the understanding of glofitamab and Lunsumio and their impact in both later and earlier lines of treatment, with the aim of providing robust and durable treatment outcomes for people with different types of lymphomas.
Early data from novel investigational bispecific antibodies in R/R MM (Abstracts #P962 and #S180)
In line with Roche’s commitment to improving outcomes and personalising care for people with blood cancer, the company has expanded beyond lymphoma and leukaemia, evaluating two investigational medicines in MM. This is the third most common type of blood cancer, diagnosed in more than 170,000 people around the world each year and involves plasma cells (antibody-producing cells in the bone marrow).[7,8] Although advances in treatment have improved outcomes, MM remains an incurable disease characterised by multiple relapses, with an overall five-year survival rate of about 55%.[9] Roche is presenting data at EHA on cevostamab, an investigational FcRH5xCD3 T-cell engaging bispecific antibody that is being evaluated as a monotherapy and in combination with other medicines to treat people with R/R MM, and on RG6234, a novel GPRC5DxCD3 T-cell engaging bispecific antibody that is being studied in a phase I trial in people with R/R MM. While early, the clinical activity and safety profiles observed with these molecules look encouraging and support further exploration.[10,11]