Mosunetuzumab Meets Primary Endpoint of Phase II Trial in Relapsed or Refractory Follicular Lymphoma

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The bispecific antibody mosunetuzumab achieved deep and durable remissions as monotherapy in patients with relapsed or refractory follicular lymphoma, according to the results of a pivotal phase II trial presented at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition.1 In a single-arm study, 80% of patients responded to mosunetuzumab, and 60% experienced a complete remission, which is much higher than that achieved by other treatments in this setting.

Laurie H. Sehn, MD, MPH

Laurie H. Sehn, MD, MPH

L. Elizabeth Budde, MD, PhD

L. Elizabeth Budde, MD, PhD

These results for an off-the-shelf T-cell engager were hailed as “potentially transformative” and “shifting the paradigm” by press conference moderator Laurie H. Sehn, MD, MPH, of the University of British Columbia, Vancouver, Canada.

“This is a very efficacious, very safe drug, even for subgroups of patients who typically do not respond well to existing therapies,” said L. Elizabeth Budde, MD, PhD, of the City of Hope Comprehensive Cancer Center in California. “The results are a strong endorsement of the unique mechanism of action for this drug.”

“This pivotal phase II study of mosunetuzumab met the primary endpoint, with a complete response rate of 60%. This is the first T-cell engager bispecific antibody to demonstrate high responses in relapsed or refractory follicular lymphoma in a phase I/II trial, and it is a promising off-the-shelf outpatient therapy,” Dr. Budde stated.


Follicular lymphoma is characterized by recurrent relapses, and the response and duration of response decrease with each successive treatment line of conventional agents, typically more chemotherapy. Refractory disease and disease progression within 24 months of therapy are associated with a poor prognosis. Mosunetuzumab is a CD20 x CD3 bispecific antibody that has one CD20 binding site to B cells and one site that engages the CD3 T cell, redirecting T cells to eliminate malignant B cells.

“By contrast with CAR T cells [another T-cell approach], mosunetuzumab is an off-the-shelf product with a fixed duration of treatment. It’s one and done,” Dr. Budde told listeners at a press conference where this presentation was highlighted.

The phase I study preceding this pivotal phase II study showed activity and manageable safety in relapsed or refractory follicular lymphoma.

Study Details

The single-arm phase II extension study Dr. Budde presented included 90 patients with grades 1 to 3a follicular lymphoma treated with at least two prior regimens, including an anti-CD20 antibody and at least one alkylating agent. Other prior therapies included anthracyclines (82.2%), autologous stem cell transplantation (21.1%), phosphoinositide 3-kinase (PI3K) inhibitors (18.9%), immunomodulating drugs (14.4%), Bruton’s tyrosine kinase (BTK) inhibitors (6.7%), and chimeric antigen receptor (CAR) T-cell therapy (3.3%).

Mosunetuzumab was given intravenously every 3 weeks, except in cycle 1 to allow for step-up dosing on days 1 to 15. “This was done to mitigate the development of cytokine-release syndrome,” she explained.

The primary endpoint was complete response as best response assessed by PET/CT imaging by independent review. If a patient achieved a complete response after eight cycles, therapy was stopped. Those with a partial response or stable disease at cycle 8 could receive up to 17 cycles of mosunetuzumab. Hospitalization was not mandatory in the protocol.

At baseline, the median age of patients was 60 years (range, 29–90 years); 61.1% were male, 58.9% had an Eastern Cooperative Oncology Group performance status of 0; 24% had stage I or II disease and 76% had stage III or IV disease. The median number of prior therapies was 3 (range, 2–10 therapies). More than three-quarters (78.9%) were refractory to any prior anti CD20 therapy, and 53.3% were refractory to both anti-CD20 therapy and alkylator therapy. A total of 52% had disease progression within 24 months.

Key Findings

At a median follow-up of 18 months, complete response rate (the primary endpoint) was 60%, “which is significantly higher than historical complete response rates of 14% with other therapies in the relapsed or refractory setting,” Dr. Budde told listeners. Secondary endpoints were objective response rate, duration of response, progression-free survival, and safety and tolerability.

The objective response rate was 80%. Response rates were comparable in all subgroups, including age, number of prior lines of therapy, response to last therapy, and high-risk subgroups (ie, double refractory and progression of disease within 24 months of first therapy). “This suggests mosunetuzumab activity in these difficult-to-treat patients,” Dr. Budde emphasized.

“About 1 year after treatment, more than 60% of those who responded and 76% of those with a complete response experienced no complications or cancer progression,” she said. A waterfall plot showed that nearly all patients achieved some degree of response.

Median duration of response in those who responded was 22.8 months. Median progression-free survival was 17.9 months. The 12-month event-free survival rate was 62%. Median time to first response was 1.4 months, and median time to first complete response was 3 months.

Safety and Tolerability

Mosunetuzumab had a manageable safety profile, and patients did not require hospitalization. All patients had an adverse event of any grade, and 92.2% had treatment-related adverse events. The rate of grade 3 or 4 adverse events was 70%, and 51.1% of those were considered related to treatment. Two grade 5 events considered unrelated to study treatment were reported.

Adverse events leading to discontinuation of treatment were uncommon (4.4%). Discontinuation of therapy due to treatment-related adverse events was reported in 2.2%. Cytokine-release syndrome of any grade occurred in 44.4% of patients, and all but two cases were of a low grade, and all cases were reported to be manageable and reversible. No patient with cytokine-release syndrome had to be hospitalized.

Median time to the onset of cytokine-release syndrome was 5.2 days. Median duration of cytokine-release syndrome was 3 days. Tocilizumab was given to 7.8% of those who had cytokine-release syndrome, and corticosteroids were given to 11.1%. Most cytokine-release syndrome events occurred during cycle 1.

Immune effector cell–associated neurotoxicity syndrome was reported in 4.4% of patients (grade 1 or 2, no grade 3). Neutropenia occurred in 28.9%; grade 3 or 4 neutropenia was reported in 26.7%. There was no reported case of febrile neutropenia. Serious adverse events included grade 3 or 4 infection in 14.4%, the most common of which was urinary tract infection (3.3%).

“The goal is not only to treat the lymphoma, but to improve patients’ quality of life. By motivating our immune system to recognize lymphoma cells, this drug may give us an opportunity for chemotherapy-free treatment of follicular lymphoma,” Dr. Budde stated. 

DISCLOSURE: Dr. Sehn has received research funding from Teva and Roche/Genentech; and has served as a consultant to Novartis Genmab, Debiopharm, Teva, Roche/Genentech, AbbVie, Acerta, Amgen, Apobiologix, AstraZeneca, Celgene, Gilead, Incyte, Janssen, Kite, Karyopharm Therapeutics, Lundbeck, Merck, MorphoSys, Sandoz, Seattle Genetics, Takeda, TG Therapeutics, and Verastem. Dr. Budde has received research funding from Merck, Amgen, AstraZeneca, and Mustang Bio; and has served as a consultant to Novartis, Gilead, F Hoffmann–LaRoche Ltd, BeiGene, and Genentech.


1. Budde LE, Sehn LH, Matasar M, et al: Mosunetuzumab monotherapy is an effective and well-tolerated treatment option for patients with relapsed/refractory follicular lymphoma who have received ≥ 2 lines of therapy: Pivotal results from a phase I/II study. 2021 ASH Annual Meeting & Exposition. Abstract 127. Presented December 11, 2021.

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