Mosunetuzumab Monotherapy Generates Promising Responses in Relapsed/Refractory Follicular Lymphoma

Single-agent mosunetuzumab (Lunsumio) produced a complete response (CR) rate that was greater than what has been observed with historical controls in patients with relapsed/refractory follicular lymphoma who had received at least 2 prior lines of therapy, meeting the primary end point of the expansion portion of the phase 1/2 GO29781 trial (NCT02500407).¹

Findings presented at the 2022 Pan Pacific Lymphoma Conference showed that mosunetuzumab elicited an overall response rate (ORR) of 80% (95% CI, 70%-88%) per independent review facility in patients enrolled to the trial (n = 90), with a CR rate of 60% (95% CI, 49%-70%). Additionally, the investigator-assessed ORR and CR rates reported with the agent were 78% (95% CI, 68%-86%) and 60% (95% CI, 49%-70%), respectively.

Notably, ORRs achieved with mosunetuzumab were comparable in high-risk subgroups, including those with double-refractory disease (n = 48) and those who experienced disease progression within 24 months from initiation of the first anti-CD20–containing chemotherapy (POD24; n = 47), at 71% (95% CI, 56%-83%) and 85% (95% CI, 72%-94%), respectively.

“Mosunetuzumab is the first T-cell–engaging bispecific antibody to demonstrate clinically meaningful outcomes for patients with relapsed/refractory follicular lymphoma in a pivotal phase 2 setting with potentially promising off-the-shelf, outpatient therapy,” lead study author Elizabeth Lihua Budde, MD, PhD, an associate professor in the Division of Lymphoma of Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, and colleagues, wrote in a poster presentation of the data.

Mosunetuzumab is a CD20xCD3 T-cell–engaging bispecific monoclonal antibody designed to redirect T cells to attack and eliminate B cells, including those that cause malignant disease.

In June 2022, the European Commission granted a conditional marketing authorization for mosunetuzumab for the treatment of adult patients with relapsed or refractory follicular lymphoma who have previously received at least 2 systemic therapies.² The following month, in July 2022, the FDA accepted a biologics license application and granted a priority review designation to mosunetuzumab for the treatment of patients with relapsed/refractory follicular lymphoma following at least 2 prior systemic therapies; a decision is expected by December 29, 2022.³

The European approval and FDA priority review were both supported by previously presented data from the GO29781 trial, which showed that mosunetuzumab was active and well tolerated in heavily pretreated patients with relapsed/refractory follicular lymphoma.

The expansion portion of the trial enrolled patients with grade 1 to 3a follicular lymphoma who received at least 2 prior treatment regimens that included at least 1 anti-CD20 antibody and at least 1 alkylating agent. To be eligible for enrollment, patients were also required to have an ECOG performance status of 0 or 1.

All participants received intravenous mosunetuzumab at doses of 1 mg of on day 1, 2 mg on day 8, and 60 mg on day 15 of cycle 1. In cycle 2, mosunetuzumab was administered at 60 mg on day 1. In cycle 3 and thereafter, mosunetuzumab was given at 30 mg on day 1. All cycles were comprised of 21 days.

In addition to the primary end point of CR rate, secondary end points of the expansion portion of the trial included ORR, duration of response (DOR), progression-free survival (PFS), and safety/tolerability.

Among all enrolled patients, the median age was 60 years (range, 29-90), and 61.1% were male. Most patients had an ECOG performance status of 0 (58.9%) and Ann Arbor stage III to IV disease (76.7%). The median number of prior lines of therapy received was 3 (range, 2-10), and 68.9% of patients were refractory to their last prior therapy. Additionally, 78.9% of patients were refractory to any prior anti-CD20 therapy, and 53.3% were double refractory to any prior anti-CD20 therapy and alkylator therapy. Approximately half of patients, or 52.2%, were POD24.

The data cutoff date for the trial was August 27, 2021. The median DOR with mosunetuzumab therapy was 22.8 months (95% CI, 9.7–not estimable [NE]) for all responders and 22.8 months (95% CI, 18.7-NE) in complete responders.

Moreover, in all responders, the median time to first response was 1.4 months (range, 1.1-8.9). The 12- and 18-month event-free rates were 62% (95% CI, 50%-74%) and 57% (95% CI, 44%-70%), respectively. Among complete responders, the median time to first response was 3.0 months (range, 1.1-18.9). Here, the 12- and 18-month event-free rates were 76% (95% CI, 65%-88%) and 70% (95% CI, 57%-84%), respectively.

Mosunetuzumab resulted in a median PFS of 17.9 months (95% CI, 10.1-NE).

Regarding safety, all patients experienced at least 1 adverse effect (AE) of any grade; 92.2% of patients experienced an AE related to mosunetuzumab. The rate of grade 3/4 AEs was 70%, 51.1% of which were related to the study drug. Serious AEs occurred in 46.7% of patients; 33.3% of these effects were related to mosunetuzumab. Two grade 5 AEs were reported, neither of which were related to the study treatment. AEs led to treatment discontinuation in 4 patients; 2 of these cases were noted to be due to mosunetuzumab.

The most commonly experienced AEs of any grade included cytokine release syndrome (CRS), fatigue, headache, pyrexia, hypophosphatemia, pruritus, neutropenia, hypokalemia, constipation, cough, diarrhea, nausea, dry skin, and rash.

CRS events of any grade occurred in 44.4% of patients, and 95% of CRS events were grade 1/2 in severity. One patient experienced grade 3 CRS, and another patient had grade 4 CRS. CRS events primary occurred during cycle 1 of treatment with the agent.

The median time to CRS onset for the first 1-mg dose of cycle 1 was 5.2 hours (range, 1.2-23.7), and the median onset for CRS onset the first 60-mg dose on day 15 of cycle 1 was 26.6 hours (range, 0.1-390.9). The median duration of CRS was 3 days (range, 1-29). Furthermore, 11.1% of patients received corticosteroids and 7.8% were given tocilizumab (Actemra) for the management of CRS.

Notably, 4.4% of patients experienced potential immune effector cell–associated neurotoxicity syndrome (ICANS) events. All ICANS-like events were noted to be low grade and to resolve. Any-grade neutropenia and grade 3/4 neutropenia occurred in 28.9% and 26.7% of patients, respectively, with no instances of febrile neutropenia observed. Serious AEs of any-grade infections were reported in 20% of patients, including 14.4% that were grade 3/4 in severity.

References

1. Budde EL, 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 prior lines of therapy: pivotal results from a phase I/II study. Presented at: 2022 Pan Pacific Lymphoma Conference; July 18-22, 2022; Koloa, HI.
2. European Commission approves Roche’s first-in-class bispecific antibody Lunsumio for people with relapsed or refractory follicular lymphoma. News release. Roche. June 8, 2022. Accessed July 19, 2022. https://bit.ly/3H7bwDT
3. FDA grants priority review to Roche’s Lunsumio for people with relapsed or refractory follicular lymphoma. News release. Roche. July 6, 2022. Accessed July 19, 2022. https://bit.ly/3NLTZ5Z