Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that new data from its CD20xCD3 T-cell engaging bispecific antibody programme, including eight oral presentations, were presented at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition, 9-12 December 2023. Based on 32-month and 3-year follow-ups of two pivotal studies for fixed-duration treatments of Columvi® (glofitamab) and Lunsumio® (mosunetuzumab), respectively, data show that remissions were maintained in the majority of patients with heavily pre-treated lymphomas.1,2 Additionally, new early-phase data of novel Columvi or Lunsumio combination regimens support ongoing investigation in Phase III studies in earlier lines of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).3,4,5,6

“Updated data from pivotal studies of Columvi and Lunsumio continue to provide compelling evidence for how fixed-duration therapies can deliver sustained, long-term benefit for people with difficult-to-treat lymphomas,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Our data at ASH also demonstrate progress in evaluating our bispecific antibodies in earlier stages of disease and additional types of lymphoma so more people can benefit from our therapies.”

Longer follow-up data from pivotal studies of fixed-duration Columvi and Lunsumio show benefit is maintained beyond the end of treatment

Extended follow-up data from the pivotal Phase II NP30179 study of Columvi administered for up to 12 cycles (approximately eight months) in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who have received at least two prior lines of therapy showed favourable long-term outcomes. After a median follow-up of 32 months, 55% of patients with a complete response (CR) were in remission at 24 months. Most of these patients remained progression-free and alive 18 months after completing the fixed-duration treatment. In patients who had received prior chimeric antigen receptor (CAR) T-cell therapy, the median duration of CR was 22.0 months (95% confidence interval [CI]: 6.7–not reached). No new safety signals were observed since the previous analysis.1

Data from a three-year follow-up analysis of the pivotal Phase II GO29781 study of Lunsumio in patients with R/R FL who have received at least two prior lines of therapy were presented. Results showed continued durable responses and a manageable safety profile after treatment (up to approximately 12 months), with 59% of patients completing treatment after eight cycles (approximately five months). 72.7% of the patients with a CR were alive and without disease progression, 30 months after their first response. In the overall population, median progression-free survival (PFS) was 24 months (95% CI: 12.0–not evaluable [NE]) and overall survival (OS) was not yet reached. No new safety signals were observed since the previous analysis.2

Additional data presented reinforce the potential of novel combination regimens in earlier treatment settings

Diffuse large B-cell lymphoma
Data from the Phase Ib/II GO40516 study of Lunsumio plus Polivy® (polatuzumab vedotin) in patients with R/R LBCL were presented and simultaneously published in Nature Medicine.3,7 Results showed that at 24 months median follow-up, the median PFS was 11.4 months (95% CI: 6.2–18.7), and median OS was 23.3 months (95% CI: 14.8–NE), highlighting the combination’s potential in R/R LBCL. The overall safety profile of patients with R/R LBCL treated with Lunsumio plus Polivy was manageable. Cytokine release syndrome (CRS) events were generally low grade (Grade 1: 10.2%; Grade 2: 5.1%; Grade 3: 3.1%).3 Lunsumio in combination with Polivy is being evaluated as an outpatient therapy for patients with R/R DLBCL in the ongoing Phase III SUNMO study.

Results from both arms of the Phase Ib NP40126 study evaluating Columvi in combination with MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), and Columvi in combination with Polivy plus MabThera/Rituxan, cyclophosphamide, doxorubicin and prednisone (Pola+R-CHP) in previously untreated DLBCL were presented. After a median of 12 months follow-up, data from the Columvi plus Pola+R-CHP arm showed that 91.7% of patients had a CR with no progression observed. Of the patients with a CR, 95.5% were still in remission, with a 12-month PFS rate of 91.5%. Safety profiles were highly consistent with earlier analyses from this study.4 These data support the ongoing Phase III SKYGLO study in previously untreated DLBCL.

Follicular lymphoma
The Phase II MorningSun study, evaluating a subcutaneous (SC) formulation of Lunsumio in patients with selected B-cell non-Hodgkin lymphomas, showed that SC Lunsumio is active and has a manageable safety profile in patients with first-line (1L) low-tumour burden FL. Data showed that 83.3% of patients achieved a complete metabolic response (95% CI: 62.6-95.3) and responses were ongoing at data cut-off. CRS was generally low grade (Grade 1: 36.7%; Grade 2: 6.7%) and occurred in cycle one only.5 Subcutaneous Lunsumio is also being investigated in combination with oral lenalidomide in 1L FL in the Phase Ib/II CO41942 study. New data demonstrated promising efficacy and manageable safety; data showed that 89.2% of patients achieved a CR and CRS events were either Grade 1 (47.5%) or 2 (2.5%), all of which were confined to cycles one to two.6 The data support further investigation of this SC formulation of Lunsumio and highlight its potential as a tailored monotherapy or combination outpatient therapy for FL, including in community practices.5,6

Totality of data presented underscores the strength of Roche's broad, industry-leading development programme, which aims to address the diverse needs, preferences and experiences of people with blood cancers

Both Columvi and Lunsumio are being investigated in Phase III studies that will expand the understanding of their impact in earlier lines of treatment. This includes the Phase III STARGLO study evaluating Columvi in combination with GemOx in patients with R/R DLBCL who are ineligible for autologous stem cell transplant; the Phase III SKYGLO study evaluating the efficacy and safety of Columvi plus Pola+R-CHP in previously untreated DLBCL; the Phase III GLOBRYTE study evaluating Columvi monotherapy in R/R mantle cell lymphoma; the Phase III SUNMO study investigating Lunsumio plus Polivy in R/R DLBCL; and the Phase III CELESTIMO study investigating Lunsumio plus lenalidomide in patients with R/R FL.