A novel bispecific antibody demonstrated durable complete responses in patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL), including those who had relapsed after chimeric antigen receptor (CAR) T-cell therapy, according to data presented at the American Society of Hematology (ASH) Annual Meeting and Exposition.

Mosunetuzumab, a fully humanized immunoglobulin G1 (IgG1) bispecific antibody targeting both CD3 and CD20, was evaluated in patients with R/R NHL, including those who previously received CAR T-cell therapy.

“When we approach unmet needs in medicine, we solve one and we create another,” lead author Stephen J Schuster, MD, said in a press briefing about the findings. CAR T cells have been a major advance in the therapy of patients with refractory B-cell malignancies, successfully treating one-third of patients. However, the other two-thirds of patients who don’t respond to CAR T-cell therapy represent a new unmet need. In addition, new treatment options are needed for patients whose disease is progressing quickly and cannot wait for CAR T cell manufacturing.

In a media preview prior to the meeting, Robert A. Brodsky, MD, secretary of ASH, emphasized the importance of the findings, noting that mosunetuzumab addresses these obstacles.

“It is an off-the-shelf product,” Brodsky explained in the briefing. “It completely gets around the problem of time to generate the CAR T-cell product.”

At the meeting, study results were presented from the ongoing phase 1/1b dose escalation study. Data was presented from Group B,  in which mosunetuzumab is administered with step-up dosing on days 1, 8, and 15 of cycle 1, and then as a fixed dose on day 1 of each subsequent 21-day cycle. The updated results include data from 270 patients with R/R NHL, which includes 30 patients with prior CAR T-cell therapy.

Overall, mosunetuzumab demonstrated durable complete response (CR) in both aggressive and indolent NHL, as well as promising CR rates in late-line diffuse large B-cell lymphoma/transformed follicular lymphoma (FL) and FL and in high-risk subsets. Pooled data from 2.8 mg to 40 mg cohorts showed an ORR of 37.1% and CR rate of 19.4% in patients with aggressive lymphoma. In those with indolent NHL, data from the 2.8 mg to 13.5 mg cohorts showed an ORR of 62.7% and a CR rate of 43.3%.

In patients with prior CAR T-cell therapy, objective responses without unexpected toxicities were observed. Mosunetuzumab demonstrated a 38.9% ORR and a 22.2% CR rate in these patients, according to the data.

With a median follow-up of 6 months since first complete remission, 83% of patients who achieved complete remissions of their slow-growing lymphomas and 71% of patients who achieved complete remissions of their fast-growing lymphomas remain free of disease.

“What I think is important is that this is not an ongoing therapy forever,” Schuster said. “This is a therapy patients receive until they’re in remission and it’s discontinued.”

Three-quarters of the patients in complete remission in this study are currently off therapy and being followed, according to Schuster.

Additionally, 4 patients in the study have been re-treated with mosunetuzumab. Three out of 4 of them responded to re-treatment, with 1 demonstrating a complete response.

Twenty-nine percent of patients in the study treated with mosunetuzumab experienced cytokine-release syndrome that was mostly mild. Four percent of patients experienced moderately severe neurologic adverse effects.

The results indicate that, as a single agent, mosunetuzumab exhibits a promising efficacy potential with acceptable risks, Schuster said. A study of higher dose mosunetuzumab is now enrolling patients. Schuster noted that long-term follow-up will help to better evaluate the durability of response data.

“There’s a lot of studies going on and I think the future for this drug and this approach, this off-the-shelf approach to exploiting cellular therapy, is the direction that we’ll be pursuing in the future,” Schuster concluded.

References
  1. Schuster SJ, Bartlett NL, Assouline S, et al. Mosunetuzumab induces complete remissions in poor prognosis non-Hodgkin lymphoma patients, including those who are resistant to or relapsing after chimeric antigen receptor T-cell (CAR-T) therapies, and is active in treatment through lines [abstract 6]. Presented at: ASH Annual Meeting and Exposition. December 7-10, 2019. Orlando, Florida.