Mosunetuzumab showed promising results in complete response rate in patients with follicular lymphoma.
Mosunetuzumab met the primary endpoint of complete response rate (CR) in patients with follicular lymphoma in a phase 2 trial. During a presentation at the Society of Hematologic Oncology Conference, Loretta Nastoupil, MD, director of the Lymphoma Outcomes Database at MD Anderson Cancer Center, noted that among participants in the phase 2 trial, all of whom received at least 2 prior treatment regimens, 60% experienced a CR.
Key secondary endpoints of the trial included overall response rate (ORR), duration of response (DoR), progression-free survival (PFS), safety, and tolerability. Nastoupil said that the trial’s dosing was unique because patients who experienced a complete CR could stop taking mosunetuzumab after 8 cycles of treatment.
“This does appear to be a very promising bispecific agent,” Natoupil said in the presentation. “Responses were deep and durable.”
Mosunetuzumab is a bispecific antibody that treats follicular lymphoma by targeting the CD20 protein on B cells and CD3 on the surface of T cells. Follicular lymphoma is characterized by recurrent disease relapse, and the progression of disease within 24 months (POD24) that is often experienced by patients has been associated with a poor prognosis.
Nastoupil’s presentation outlined the findings of mosunetuzumab in the trial, which studied the safety and efficacy of the drug on patients with follicular lymphoma. In this trial, more than half of all patients had a POD24 and a median of 3 prior therapies.
In the trial, 90 patients received different doses of mosunetuzumab monotherapy during a 21-day cycle. The dose slowly increased to mitigate a dangerous inflammatory cytokine release system (CRS) response. It increased from 1 mg to 2 mg by day 8, and to 60 mg (the highest dose) on day 15 of cycle 1 and day 1 of cycle 2. For the rest of the cycles, dosage decreased and plateaued at 30 mg.
According to Nastoupil, 80% of participants met the key secondary endpoint of ORR. The median DoR was 22.8 months, whether that was CR or some other type. Further, median PFS was 17.9 months, and the median time to first response was 1.4 months.
“When we look across the subgroups, it appears that all subgroups tended to have favorable responses, including those patients that were double refractory or had a POD24 status,” Nastoupil said in her presentation.
Among participants, 51% experienced grade 3 or higher adverse events (AEs)—however mosunetuzumab did not cause any fatalities and is considered to have a tolerable safety profile. CRS was one of the most common AEs, but it appeared to only affect patients during cycle 1. Other AEs include fatigue, headache, pyrexia, hypophosphatemia, and neutropenia (AE of grade 3 or higher).
“There was excellent concordance between the Investigative Review Committee and the investigator,” Nastoupil concluded. “The toxicity profile appears to be very favorable…and most patients can receive this in an outpatient setting,”
The FDA is expected to decide on the approval of mosunetuzumab within the next few months.
Nastoupil, Loretta. Mosunetuzumab Monotherapy is an Effective and Well-Tolerated Treatement Opiton for Patients with Relapses/Refractory (R/R) Follicular Lymphoma (FL) who have Received ≥ Prior Lines of Therapy: Pivotal Results from a Phase I/II Study. Society of Hematologic Oncology Conference. September 30, 2022. Accessed on September 30, 2022.