Roche revealed the latest findings from its pioneering CD20xCD3 T-cell-engaging bispecific antibody program at the 66th Annual Meeting and Exposition of the American Society of Hematology (ASH), held from December 7-10, 2024. More than 20 abstracts featuring bispecific antibodies were presented, highlighting the efficacy of fixed-duration Columvi (glofitamab) and Lunsumio (mosunetuzumab) across various types of aggressive and indolent lymphomas. These presentations align with Roche’s commitment to innovating patient treatments by refining therapeutic standards at the onset of disease while examining alternative administration methods to enhance patient experience.
“The data exhibited at ASH reaffirm that Columvi and Lunsumio can result in prolonged remissions for those battling advanced lymphoma,” expressed Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “Our endeavors aim to revolutionize the treatment landscape for B-cell malignancies by providing a spectrum of groundbreaking therapeutic options.”
Elizabeth Budde, M.D., Ph.D., Executive Medical Director of the Enterprise Immune Effector Cell Program at City of Hope, remarked on the broader challenges faced by lymphoma patients, stating, “Apart from the clinical hardships, patients endure both physical and emotional strain due to frequent appointments and treatments.” She noted that while Lunsumio’s fixed-duration intravenous formulation has already delivered a substantial treatment alternative, the potential addition of a subcutaneous route could abbreviate administration times. The availability of diverse treatment routes empowers patient-specific therapy adjustments, fostering a personalized approach in follicular lymphoma care.
Follow-up from the pivotal phase II NP30179 study: Three years later, Columvi was shown to produce a complete response (CR) in 40% of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL), with CR duration averaging 29.8 months (95% CI: 22.0–not estimable [NE]). Patients maintaining remission post-therapy completion largely remained so after two years. Safety assessments aligned with prior evaluations.
In the four-year follow-up from the pivotal phase II GO29781 study on Lunsumio, there were significant remissions observed, with 64% (95% CI: 50.1-78.0) of patients with a CR remaining alive and free from disease progression at 45 months. The overall response rate (ORR) and CR for the entire population stood at 77.8% and 60.0%, respectively. Similar outcomes were noted in the cohort experiencing disease progression within 24 months of frontline treatment (POD24), which is typically challenging to treat. As with earlier analyses, no new safety signals appeared.
Both studies demonstrated B-cell levels beginning to restore between 12–18 months post-Columvi treatment and 19 months post-Lunsumio treatment, hinting at immune recovery and reinforcing the viability of a fixed-duration treatment strategy. Recovery of B cells after lymphoma treatment is essential for sustaining a functional immune system.
A US-based real-world study and economic model evaluating patient-related travel burden for R/R non-Hodgkin lymphoma across various bispecific antibody therapies highlighted travel distance, time, and costs, factors often overshadowed by clinical efficacy and safety. These variables are crucial in deciding treatment, further emphasizing the necessity for patient-centered treatment options. The study discovered that fixed-duration therapies like Columvi and Lunsumio alleviate travel burden due to less frequent dosing.
The initial analysis from the phase II GO29781 trial, which explored the subcutaneous delivery of investigational Lunsumio in patients with third-line or later follicular lymphoma was presented for the first time. Results suggested that pharmacokinetic metrics were not inferior compared to intravenous (IV) administration, with fixed-duration Lunsumio offering high rates of profound and sustained remissions. 76.6% achieved an ORR, with 61.7% attaining CR, as per independent review committee evaluation. Median progression-free survival was 23.7 months (95% CI: 14.6-NE), while median overall survival remains unattained. Common all-grade adverse events included injection-site reactions (60.6%; all Grade 1-2), fatigue (35.1%), and cytokine release syndrome (CRS; 29.8%). The CRS event rate was minimal (Grade 1-2, 27.6%; Grade 3, 2.1%), with all instances occurring during cycle 1 and resolving.4 As a result, submissions to health authorities aim to provide patients and healthcare personnel more administration options tailored to unique needs.
Emerging data from a randomized phase II cohort of the investigational GO40516 study highlighted enhanced efficacy and manageable safety of the outpatient, subcutaneously administered and fixed-duration Lunsumio combined with Polivy (polatuzumab vedotin) compared to MabThera/Rituxan (rituximab) and Polivy in patients with R/R LBCL. The Lunsumio-Polivy group exhibited a 77.5% ORR (95% CI: 61.6-89.2) versus 50.0% (95% CI: 33.8–66.2) for MabThera/Rituxan-Polivy, with a CR rate of 57.5% (95% CI: 40.9-73.0) vis-a-vis 35.0% (95% CI: 20.6-51.7). Adverse events of particular interest in ≥30% of patients included injection-site reactions (55.0%) and neutropenia (40.0%). CRS events were reported in four patients (10.0%), all classified as Grade 1-2, occurring during cycle 1 and resolving.5 These findings endorse further examination of this treatment combination in the ongoing phase III SUNMO study, which could serve as an alternative second-line option for DLBCL, addressing varied patient needs.
Updated results from the phase I/Ib investigational NP39488 study revealed high and durable responsiveness among R/R LBCL patients treated with Columvi and Polivy, including those with high-grade disease or previous CAR T-cell therapy. Among 128 efficacy-evaluable participants, there was an 80.6% best ORR alongside a 62.0% CR rate, with CR durations averaging 31.8 months (95% CI: 21.9-NE). For patients with previous CAR T-cell therapy (n=28), the ORR was 75.0%, with a CR rate at 50.0%. The safety profile appeared manageable and consistent with known individual drug profiles, the most common AE being Grade 1-2 CRS (44.4%).6 Results affirm continued development of this investigational combination in the phase III SKYGLO study, examining Columvi alongside Polivy-MabThera/Rituxan, cyclophosphamide, doxorubicin, and prednisone (R-CHP) in newly-diagnosed DLBCL.
Columvi is designed as a CD20xCD3 T-cell-engaging bispecific antibody that targets CD3 on T cells and CD20 on B cells. It features a novel 2:1 structural design, with one region targeting CD3 on T cells, a type of immune cell, and two regions binding to CD20 on B cells, which may be either healthy or cancerous. This dual-targeting brings the T cell close to the B cell, initiating the release of cell-killing proteins. Roche is exploring Columvi as a standalone therapy and in conjunction with other medications for diffuse large B-cell lymphoma and mantle cell lymphoma.
Lunsumio is heralded as a first-in-class CD20xCD3 T-cell-engaging bispecific antibody devised to target CD3 on T cells and CD20 on B cells. This dual-targeting stimulates and redirects a patient’s existing T cells to engage and obliterate target B cells by releasing cytotoxic proteins into the B cells. A robust clinical development program for Lunsumio is underway, assessing it as a monotherapy and with other treatments for individuals with B-cell non-Hodgkin lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, as well as other blood cancers.
Polivy is innovatively designed as an anti-CD79b antibody-drug conjugate (ADC). With CD79b protein being prevalent in most B cells, a type impacted by some non-Hodgkin lymphomas (NHL), it represents a prime target for groundbreaking therapies. Polivy connects with and eradicates B cells expressing CD79b via targeted anti-cancer agents, reputedly minimizing harm to normal cells. Developed by Roche using Pfizer ADC technology, Polivy is currently under investigation for treating multiple NHL types.