Roche’s Lunsumio Combination Meets Primary Endpoint in Phase III CELESTIMO Trial for Relapsed or Refractory Follicular Lymphoma
Roche has announced positive topline results from the Phase III CELESTIMO study evaluating Lunsumio® (mosunetuzumab) in combination with lenalidomide in people with relapsed or refractory (R/R) follicular lymphoma (FL). The combination achieved the study’s primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with MabThera®/Rituxan® (rituximab) plus lenalidomide.
The findings represent an important development in Roche’s efforts to expand the use of Lunsumio into earlier lines of treatment for follicular lymphoma. CELESTIMO enrolled patients with R/R FL who had received at least one previous line of therapy and was designed to compare the Lunsumio-based combination with a commonly used rituximab-based regimen.
At the time of the interim analysis, overall survival (OS) data remained immature, meaning there were not yet enough events to make a definitive assessment of the treatment’s effect on overall survival. Roche said additional data from CELESTIMO will be submitted to health authorities and presented at a future medical meeting.
The safety profile observed with Lunsumio and lenalidomide was consistent with the established safety profiles of the individual medicines. No new safety signals were identified during the study.
CELESTIMO Shows Significant Progression-Free Survival Benefit
The Phase III CELESTIMO trial was designed to evaluate whether combining Lunsumio, a CD20xCD3 bispecific antibody, with lenalidomide could improve outcomes compared with rituximab plus lenalidomide in patients with previously treated follicular lymphoma.
According to Roche, the study met its primary endpoint by showing a statistically significant and clinically meaningful improvement in PFS for patients receiving the Lunsumio-based combination.
PFS is an important endpoint in follicular lymphoma because the disease is generally characterized by periods of response and remission followed by relapse or progression. Delaying disease progression can potentially provide patients with longer periods without worsening disease and the need for another line of treatment.
The CELESTIMO findings therefore provide clinical evidence supporting further evaluation of Lunsumio and lenalidomide as a treatment option for patients whose follicular lymphoma has returned or stopped responding to previous therapy.
While the PFS results were positive, Roche noted that OS data were immature at the time of the interim analysis. Continued follow-up will be needed to establish whether the observed PFS benefit ultimately translates into a measurable difference in overall survival.
Potential Expansion Into Earlier-Line Follicular Lymphoma
Lunsumio is already approved in multiple countries for people with follicular lymphoma who have received three or more prior lines of therapy. CELESTIMO is particularly significant because it is intended to support expansion of Lunsumio into an earlier treatment setting.
Roche described CELESTIMO as a confirmatory study required to convert the accelerated approval in the United States and conditional marketing authorization in certain regulatory jurisdictions for Lunsumio monotherapy in third-line or later (3L+) follicular lymphoma into full approval.
The study is also intended to support a potential indication for Lunsumio in second-line or later (2L+) follicular lymphoma.
Moving an established therapy into earlier treatment settings can potentially make the medicine available to a larger population of patients. For Roche, the CELESTIMO results provide an important clinical milestone as the company seeks to expand the role of Lunsumio in the treatment sequence for B-cell malignancies.
Roche Highlights Outpatient Treatment Potential
Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development, said patients with R/R follicular lymphoma need treatment options that can provide meaningful clinical benefits while minimizing disruptions to everyday life.
Garraway said the CELESTIMO results indicate that a two-drug outpatient regimen based on Lunsumio could potentially offer an effective treatment option earlier in the disease journey.
The outpatient potential of Lunsumio is an important part of Roche’s development strategy for the medicine. Treatment administration and healthcare resource requirements can have a significant impact on patients, caregivers and healthcare systems, particularly when therapies are administered repeatedly over long periods.
Lunsumio has also been developed with flexibility in administration in mind, offering both intravenous and subcutaneous administration routes. Roche said these features are intended to address different patient and healthcare provider preferences while supporting more convenient treatment delivery.
Lunsumio’s CD20xCD3 Bispecific Mechanism
Lunsumio is part of Roche’s broader CD20xCD3 bispecific antibody programme. The medicine is designed to recognize CD20 on B cells and CD3 on T cells, bringing the two cell types together to facilitate an immune-mediated response against malignant B cells.
Bispecific antibodies have become an increasingly important area of development in B-cell malignancies, offering an alternative approach to engaging the immune system against cancer cells.
Roche has been developing Lunsumio across multiple lymphoma settings, including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). The company said the medicine has accumulated the longest follow-up data of any bispecific antibody in lymphoma, reflecting the breadth and duration of its clinical development programme.
Lunsumio is currently approved for people with 3L+ follicular lymphoma in 60 countries worldwide and has been used to treat more than 3,800 patients, according to Roche.
The existing clinical and commercial experience provides a foundation for the company’s efforts to investigate the medicine in earlier lines of treatment and additional B-cell malignancies.
Combination Strategy With Lenalidomide
The CELESTIMO study evaluates Lunsumio in combination with lenalidomide. Lenalidomide is an immunomodulatory medicine that has been used in the treatment of several hematologic malignancies, including follicular lymphoma.
Combining different therapeutic mechanisms is an established strategy in lymphoma treatment, with the goal of improving disease control while maintaining a manageable safety profile.
In CELESTIMO, the Lunsumio-plus-lenalidomide combination was compared against rituximab plus lenalidomide. The trial therefore provides a direct evaluation of a bispecific-antibody-based regimen against a CD20-directed antibody combination in previously treated FL.
The positive PFS result supports continued investigation of this treatment strategy and provides evidence for Roche’s regulatory plans involving earlier-line disease.
At the same time, the immature OS data mean that longer follow-up will be necessary to determine the impact of the treatment on survival outcomes.
Safety Profile Remains Consistent
Safety remains an important consideration as Lunsumio moves into earlier treatment settings and combination regimens.
Roche reported that the safety profile of the Lunsumio and lenalidomide combination in CELESTIMO was consistent with the known safety profiles of the individual study medicines. No new safety signals were identified during the interim analysis.
The company will provide additional clinical data at a future medical meeting and submit the CELESTIMO results to relevant health authorities as part of the regulatory process.
Further analyses are expected to provide a more detailed understanding of the treatment’s efficacy and safety, including additional follow-up on overall survival.
Broader Development Across B-Cell Malignancies
The CELESTIMO findings form part of Roche’s broader strategy to develop Lunsumio across different stages and types of B-cell malignancies.
In addition to its follicular lymphoma programme, Lunsumio is being evaluated in DLBCL. The U.S. Food and Drug Administration recently accepted Roche’s supplemental Biologics License Application (sBLA) for Lunsumio in combination with Polivy® (polatuzumab vedotin) for second-line or later DLBCL.
The application is based on results from the SUNMO study, which is evaluating the Lunsumio and Polivy combination in patients with previously treated DLBCL.
The company is also continuing to investigate Lunsumio and lenalidomide in earlier-stage follicular lymphoma. The Phase III MorningLyte study is ongoing in first-line FL, extending the clinical development programme into the initial treatment setting.
This development strategy could potentially position Lunsumio across multiple points in the treatment journey, from later-line disease through earlier treatment settings.
Next Steps for CELESTIMO
The positive CELESTIMO result represents an important milestone for Roche’s Lunsumio development programme. The achievement of the primary PFS endpoint provides clinical evidence supporting the combination of mosunetuzumab and lenalidomide in patients with R/R follicular lymphoma who have received at least one previous line of treatment.
However, the interim analysis does not yet provide mature overall survival data. Continued monitoring will therefore be important to determine longer-term outcomes.
Roche plans to submit the CELESTIMO results to health authorities and present the detailed findings at an upcoming medical meeting. Those data are expected to provide further information on the magnitude and durability of the PFS benefit, as well as additional safety findings.
For patients with relapsed or refractory follicular lymphoma, the results add to the growing body of evidence supporting bispecific antibodies as an emerging treatment approach in B-cell cancers. For Roche, the findings also strengthen efforts to move Lunsumio beyond its current 3L+ indication and evaluate its potential role earlier in the treatment pathway.
With CELESTIMO demonstrating a statistically significant and clinically meaningful PFS improvement, the company is now positioned to advance discussions with regulators while continuing clinical development of Lunsumio across follicular lymphoma and DLBCL. The ongoing MorningLyte and other studies will further determine how the medicine could fit into future treatment strategies across different stages of B-cell malignancies.
About the CELESTIMO study
CELESTIMO [NCT04712097] is a phase III trial evaluating the efficacy and safety of Lunsumio® (mosunetuzumab) in combination with lenalidomide vs. MabThera®/Rituxan® (rituximab) plus lenalidomide in people with relapsed or refractory follicular lymphoma (FL) who have received at least one line of prior systemic therapy. It is a confirmatory study required to convert the accelerated approval/conditional marketing authorisation of Lunsumio monotherapy for third-line or later FL to full approval, as well as to secure an indication in second-line or later FL.
About follicular lymphoma
Follicular lymphoma (FL) is the most common slow-growing (indolent) form of non-Hodgkin lymphoma, accounting for about one in five cases.2 It typically responds well to treatment but is often characterised by periods of remission and relapse.3 The disease typically becomes harder to treat each time a patient relapses, and early progression can be associated with poor long-term prognosis.4 It is estimated that more than 110,000 people are diagnosed with FL each year worldwide.5
About Lunsumio® (mosunetuzumab)
Lunsumio is a first-in-class CD20xCD3 T-cell engaging bispecific antibody 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 malignant B cells. Lunsumio is currently approved as a fixed-duration monotherapy for the treatment of adult patients with third-line or later relapsed or refractory follicular lymphoma (FL) in both intravenous and subcutaneous (Lunsumio VELO™) formulations. A robust, global development programme is ongoing to explore the clinical utility of Lunsumio earlier in the disease course and in novel combinations, including the phase III CELESTIMO trial in second-line or later FL.
About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for more than 25 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases.
Our approved medicines include MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab), PiaSky® (crovalimab), Lunsumio® (mosunetuzumab) and Columvi® (glofitamab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibody cevostamab, targeting both FcRH5 and CD3. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.
About Roche
Roche (SIX: RO, ROP; OTCQX: RHHBY) is a healthcare company uniquely placed to prevent, stop and cure diseases by uniting leading science and technology across diagnostics, medicines and digital solutions.
Roche was founded in Basel, Switzerland in 1896 and today is a leading provider of transformative medicines and diagnostics for millions of people in over 150 countries around the world. It is dedicated to tackling healthcare challenges that place the greatest strain on patients, families, communities and healthcare systems. Across its Diagnostics and Pharmaceutical divisions, Roche focuses on areas including oncology, neurology, cardiovascular and metabolic diseases, ophthalmology, infectious diseases and immunology with the aim of providing real and positive change for patients, the people they love and the professionals who care for them.
Genentech in the United States is a fully owned subsidiary in the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, a major innovator in the Japanese therapeutic antibody market.