European Fee Approves Mosunetuzumab for Sufferers with R / R Follicular Lymphoma
Conditional advertising and marketing authorization has been granted to the CD20xCD3 T-cell participating bispecific antibody mosunetuzumab (Lunsumio) by the European Fee for the therapy of grownup sufferers with relapsed or refractory follicular lymphoma who’ve beforehand acquired no less than 2 prior systemic therapies, based on Roche.1
The premise of the approval is supported by findings of the section 1/2 GO29781 trial (NCT02500407), which met its main finish level of full response (CR) per impartial evaluation facility (IRF) evaluation in 2021, with the bispecific antibody eliciting a CR price of 60% (95% CI, 49% -70%) at a median follow-up of 18.3 months.
Additional knowledge revealed the general response price (ORR) achieved with the agent to be 80% (95% CI, 70% -88%), and that the median length of response (DOR) was 22.8 months (95% CI, 9.7– not estimable [NE]). Together with this, favorable tolerability was seen in sufferers with closely pretreated follicular lymphoma who acquired mosunetuzumab.
“We’re delighted that Lunsumio is the primary bispecific antibody permitted in Europe for folks with relapsed or refractory follicular lymphoma,” stated Levi Garraway, MD, PhD, Roche’s chief medical officer and head of world product improvement, within the press launch. “Lunsumio’s excessive response charges, off-the-shelf availability, and preliminary outpatient administration might remodel how superior follicular lymphoma is handled.”
Inside the multicenter, open-label, dose-escalation, and dose-expansion trial, mosunetuzumab was examined in sufferers with follicular lymphoma with grade 1 to 3a illness.2
Eligibility within the trial was open to sufferers with an ECOG efficiency standing of 0 to 1 and to those that had beforehand acquired 2 or extra systemic regimens, together with no less than 1 anti-CD20 antibody and 1 alkylating agent.
Each 3 weeks, as a part of 21-day cycles via a step-up dosing strategy in cycle 1, sufferers (n = 90) had been administered mosunetuzumab. Inside the first cycle, sufferers acquired mosunetuzumab at a dose of 1 mg on day 1, 2 mg on day 8, and 60 mg on day 15. For cycle 2, mosunetuzumab was given at a dose of 60 mg on day 1. In subsequent cycles, the bispecific antibody was given at 30 mg on day 1. For the sufferers who achieved a CR following cycle 8, they had been subjected to 17 cycles of therapy. Moreover, there was no obligatory hospitalization for contributors given the preliminary dose.
The first finish level of the trial was CR price per IRF evaluation, evaluated as compared with the historic CR price of 14%, and secondary finish factors included ORR, DOR, progression-free survival (PFS), security, and tolerability.
Of these enrolled within the examine, the median age was 60 years (vary, 29-90) with 61.1% being male. Sufferers with an ECOG efficiency standing of 0 made up 58.9% of the contributors whereas 41.1% had a standing of 1. A complete of 23.3% of sufferers had stage I-II Ann Arbor illness, and 76.7% had stage III-IV illness. Moreover, these enrolled within the trial principally had acquired 3 prior traces of remedy (vary, 2-10), and all sufferers had beforehand acquired anti-CD20 remedy and an alkylator.
Different prior systemic therapies sufferers acquired consisted of PI3K inhibitors (18.9%), immunomodulatory medication (14.4%), and chimeric antigen receptor (CAR) T-cell remedy (3.3%). Sufferers who had beforehand had autologous stem cell transplant made up 21.1% of contributors.
Furthermore, 68.9% of people had been refractory to the final prior remedy they acquired, 78.9% of sufferers had been refractory to a earlier anti-CD20 remedy, and 53.3% had been double refractory to an anti-CD20 remedy in addition to an alkylating remedy. A complete of 52.2% of sufferers additionally had development of illness inside 24 months (POD24) of beginning therapy.
Knowledge offered on the 2021 ASH Annual Assembly revealed that mosunetuzumab had an investigator-assessed CR price of 60% (95% CI, 49% -70%), and the CR charges produced with the agent in high-risk subgroups had been just like that of the general examine inhabitants.
Sufferers youthful than 65 years of age (n = 60) had a CR price with the bispecific antibody of 55% (95% CI, 42% -68%) in contrast with a CR price of 70% (95% CI, 51% – 85%) in sufferers aged 65 years or older (n = 30). With the agent, the CR price was 74% (95% CI, 56% -87%) for individuals who beforehand acquired 2 traces of remedy (n = 34) and 52% (95% CI, 39% -65%) in sufferers who acquired 3 or extra prior traces (n = 56). Sufferers who had been relapsed or refractory to their final prior remedy (n = 62) and in those that weren’t (n = 28) demonstrated CR charges of 52% (95% CI, 39% -65%) and 79% (95% CI, 59% -92%), respectively.
Mosunetuzumab additionally produced a CR price of fifty% (95% CI, 35% -65%) within the group of people who had been double refractory (n = 48) vs 71% (95% CI, 55% -84%) in those that weren’t. Additional, the CR price was proven to be 57% (95% CI, 42% -72%) for these with POD24 illness (n = 47) in contrast with 63% (95% CI, 47% -77%) in those that didn’t progress inside 24 months (n = 43).
Median time to response was 1.4 months (vary, 1.1-8.9), and the median time to first CR was 3.0 months (vary, 1.1-18.9). The median PFS with mosunetuzumab was 17.9 months (95% CI, 10.1-NE).
In regard to security, cytokine launch syndrome (CRS) was the commonest toxicity, which was noticed in 39% of sufferers. Nonetheless, CRS was low grade with 14% of sufferers experiencing grade 2 CRS, and it was resolved by therapy completion. Different ceaselessly noticed hostile results included neutropenia, hypophosphatemia, pyrexia, and headache.
Two section 3 scientific research are exploring the usage of mosunetuzumab within the second-line setting: CELESTIMO (NCT04712097), investigating mosunetuzumab plus lenalidomide (Revlimid) for sufferers with follicular lymphoma, and SUNMO (NCT05171647), investigating mosunetuzumab plus polatuzumaby vedin) for sufferers with diffuse giant B-cell lymphoma.
“Having extra therapy choices for folks with follicular lymphoma, the place a number of prior traces of remedy have failed, is essential to assist them obtain higher outcomes,” Elizabeth Budde, MD, PhD, a hematologic oncologist and affiliate professor on the Metropolis of Hope Complete Most cancers Middle, added within the press launch. “It’s thrilling to have a brand new class of immunotherapy like Lunsumio, providing a available, chemotherapy-free and fixed-duration therapy, with nice potential to supply sturdy remissions with out the necessity to keep on therapy repeatedly.”
European Fee approves Roche’s first-in-class bispecific antibody Lunsumio for folks with relapsed or refractory follicular lymphoma. Information launch. Roche. June 8, 2022. Accessed June 9, 2022. https://bit.ly/3H7bwDT
Budde EL, Sehn LH, Matasar M, et al. Mosunetuzumab monotherapy is an efficient and well-tolerated therapy choice for sufferers with relapsed / refractory (R / R) follicular lymphoma (FL) who’ve acquired ≥2 prior traces of remedy: pivotal outcomes from a section I / II examine. Offered at: 2021 ASH Annual Assembly and Exposition; December 11-14, 2021; Atlanta, GA. Summary 127.