City of Hope to Conduct Phase 2 Clinical Trial of Epcoritamab and Lenalidomide Combination Therapy for Untreated Follicular Lymphoma
Challenging the Paradigm of First-Line Treatment Without Chemotherapy
This Phase 2 clinical trial (NCT06112847), led by City of Hope, a leading cancer research institution in the United States, evaluates the efficacy of the combination therapy of epcoritamab (brand name: Epkinly) and lenalidomide (brand name: Revlimid) in patients with follicular lymphoma (FL) who have not received prior treatment. Follicular lymphoma is a type of blood cancer that frequently relapses and is difficult to cure. The current standard treatment typically involves a combination of highly toxic chemotherapy and rituximab. However, due to the significant side effects, there has been a growing need for new first-line treatment options that exclude chemotherapy. The global market size for follicular lymphoma is projected to reach approximately $5.93 billion by 2026, making this trial a crucial turning point that could change the market paradigm.
Maximizing Synergy with a Bispecific Antibody and Immunomodulatory Agent
Epcoritamab is a CD20xCD3 bispecific antibody developed jointly by Genmab and AbbVie. It simultaneously binds to CD20 on the surface of cancer cells and CD3 on T cells, inducing cancer cell death. In combination with lenalidomide, an immunomodulatory drug (IMiD) from Bristol Myers Squibb, the anti-tumor effect is amplified. Lenalidomide targets the cereblon E3 ubiquitin ligase complex, promoting T-cell activation and amplifying immune function. The combination of these two mechanisms creates a synergistic effect that maximizes the durability of the immune response, improving the tumor microenvironment and significantly increasing the treatment response rate.
Innovative Clinical Design with Short-Term Administration to Reduce Toxicity
This Phase 2 trial began in January 2024 and is currently in the active, not recruiting phase, with ongoing follow-up. The primary endpoint is the complete response rate (CRR), and the secondary endpoints include overall response rate (ORR), progression-free survival (PFS), and safety, all of which will be comprehensively evaluated. Patients receive a time-limited therapy regimen, with drug administration limited to a maximum of 12 cycles, which significantly reduces cumulative toxicity. This design will be a useful alternative for elderly or frail patients who are candidates for first-line treatment.
Increasing Competition in the Blood Cancer Market and Global Approval History
Epcoritamab has already received FDA accelerated approval in June 2024 as a single-agent therapy for third-line or later relapsed/refractory follicular lymphoma, and in November 2025, it received FDA full approval as a combination therapy with lenalidomide and rituximab for the treatment of relapsed/refractory follicular lymphoma. However, this trial is differentiated in that it aims to maximize treatment convenience by using only a bispecific antibody and an immunomodulatory agent in combination in the first-line treatment setting, excluding rituximab. Currently, Roche's mosunetuzumab and glofitamab are in fierce competition in the blood cancer market. In this context, the success of epcoritamab combination therapy in entering the first-line treatment setting will be key to gaining a competitive advantage in future market share.
This Phase 2 clinical trial is a significant milestone in the follicular lymphoma market, which is projected to reach $5.93 billion by 2026, as it evaluates the clinical value of epcoritamab and lenalidomide combination therapy as a first-line treatment that completely eliminates the need for chemotherapy. Compared to the current standard treatment of rituximab-based chemotherapy, it significantly reduces cumulative toxicity and introduces a time-limited treatment design of up to 12 cycles, which can greatly improve patient compliance and quality of life. In a situation where Roche's mosunetuzumab and other competing drugs are seeking to expand their market share in the blood cancer field, the success of this trial will allow AbbVie and Genmab to strengthen their first-line treatment lineup and secure market leadership. The fact that Bristol Myers Squibb's lenalidomide will be available as a low-cost generic after patent expiration is a positive factor that will contribute to the rapid market adoption and regulatory approval of this combination therapy. In the short term, demonstrating clinical safety is key, but in the long term, the combination of immunomodulatory agents and bispecific antibodies will establish itself as the standard paradigm for first-line treatment of blood cancers, maximizing the pipeline value of related companies.
Source: ClinicalTrials.gov (api_ct)