Outpatient administration of mosunetuzumab in US community practice settings: perspectives and learnings from the Phase II MorningSun study

Abstract

Introduction: Mosunetuzumab (mosun) is a CD20xCD3 T-cell engaging bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells. The Phase II MorningSun study evaluates subcutaneous (SC) mosun in select B-cell non-Hodgkin lymphomas (B-NHLs), including follicular lymphoma (FL). As intravenous mosun is already FDA-approved for relapsed/refractory FL after ≥2 prior treatments (txs), there is also a need to understand how to manage patients (pts) at risk for cytokine release syndrome (CRS), especially in an outpatient setting. We present interim safety data from the MorningSun first-line (1L) high tumor burden FL cohort and describe the approach to monitoring/managing CRS from the community practice perspective. Methods: MorningSun is an open-label, multicenter trial of SC mosun monotherapy in B-NHL (NCT05207670). Mosun is given as step-up dosing in Cycle (C) 1 (5 mg Day [D] 1, 45 mg D8, 45 mg D15) then 45 mg on D1 of each 21-day C for up to 17 Cs (1 year) in pts with high-tumor burden 1L FL. Pts with partial/complete metabolic response may receive additional maintenance therapy. The primary endpoint in the FL cohorts is progression-free survival rate at 24 months. Secondary endpoints include safety, pharmacokinetics, time to next tx, duration of response, overall survival, and objective response rate. Prophylaxis for CRS is mandatory for the first 2 Cs and optional thereafter. Pre-tx with acetaminophen and/or diphenhydramine may also be given. The study allows for outpatient tx in academic medical centers/community practice sites. Results: Safety analyses in the high-tumor burden FL cohort were based on a cutoff date of Aug 10, 2022, at which time 23 sites were active (all non-academic community sites). Eighteen pts had completed ≥1 C of mosun, of whom 16 (88.9%) were still on tx and 2 (11.1%) had progressive disease. Median age was 64 (range 28–79) years; sex was equally balanced. With a median follow up of 2.1 months, 15 (83.3%) pts experienced ≥1 adverse event (AE). Serious AEs occurred in 4 (22.2%) pts, with Grade (Gr) ≥3 AEs in 3 (16.7%) pts. Twelve (66.7%) pts had ≥1 tx-related AE. The most common AEs (≥20%) were injection-site reaction (n = 6, 33.3%) and CRS (n = 4, 22.2%; no oxygen, steroids, tocilizumab, or vasopressors required; Table). All pts had complete resolution of CRS events and continued tx. One pt (5.6%) had 2 neurologic AEs (headache Gr 1 and insomnia Gr 2), both of which resolved. Community sites created a support network to help pts, their treating physicians, and other colleagues monitor for, identify, and manage CRS. Additional details of this process will be presented at the meeting. Conclusions: MorningSun is the first study to evaluate SC mosun in 1L FL. Early safety data support its continued evaluation in this setting. These findings, along with best practice examples, illustrate that community practices can safely manage pts receiving mosun in an outpatient setting. The research was funded by: The MorningSun study is sponsored by Genentech, Inc. Third-party medical writing assistance, under the direction of the authors, was provided by Martha Warren, MSci, and Roisin Weaver, MSc, of Ashfield MedComms, an Inizio company, and was funded by Genentech, Inc. Keywords: Immunotherapy, Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. I. W. Flinn Employment or leadership position: Sarah Cannon Research Institute, Tennessee Oncology Consultant or advisory role: consultancy - all payments made to Sarah Cannon Research Institute, not to the physician. AbbVie, BeiGene, Century Therapeutics, Genentech, Genmab, Hutchison MediPharma, InnoCare Pharma, Kite Pharma, Myeloid Therapeutics, Novartis, Secura Bio, Servier Pharmaceuticals, TG Therapeutics, Vincerx Pharma, Xencor Research funding: research grants - all payments made to Sarah Cannon Research Institute, not to the physician. AbbVie, Acerta Pharma, Agios, ArQule, AstraZeneca, BeiGene, Biopath, Bristol Myers Squibb, CALIBR, CALGB, Celgene, City of Hope National Medical Center, Constellation Pharmaceuticals, Curis, CTI Biopharma, Epizyme, Fate Therapeutics, Forma Therapeutics, Forty Seven, Genentech, Gilead Sciences, InnoCare Pharma, IGM Biosciences, Incyte, Infinity Pharmaceuticals, Janssen, Kite Pharma, Loxo, Marker Therapeutics, Merck, Millennium Pharmaceuticals, MorphoSys, Myeloid Therapeutics, Novartis, Nurix, Pfizer, Pharmacyclics, Portola Pharmaceuticals, Rhizen Pharmaceuticals, Roche, Seattle Genetics, Step Pharma, Tessa Therapeutics, TG Therapeutics, Trillium Therapeutics, Triphase Research & Development Corp., Unum Therapeutics, Verastem, Vincerx Pharma, 2 seventy bio J. Sharman Employment or leadership position: US Oncology Network Consultant or advisory role: TG Therapeutics, Genentech, Abbvie, Acerta Pharma/AstraZeneca, Beigene, Bristol-Myers Squibb, Merck Research funding: Pharmacyclics, Genentech, Celgene, Acerta Pharma, Gilead Sciences, Seattle Genetics, TG Therapeutics, Merck, Takeda S. Liu Research funding: Roche M. Gandhi Employment or leadership position: Virginia Cancer Specialists Consultant or advisory role: GSK, TG Therapeutics, Karyopharm Therapeutics, Janssen Oncology, Sanofi B. Anz Other remuneration: All disclosures to be confirmed J. M. L. Biondo Employment or leadership position: Genentech Stock ownership: Roche P. Jani Employment or leadership position: Genentech Stock ownership: Genentech Other remuneration: travel, accommodation, expenses - Genentech M. Wu Employment or leadership position: Genentech Stock ownership: Roche T. Lin Employment or leadership position: Genentech Stock ownership: Genentech Other remuneration: travel, accommodation, expenses - Genentech N. Parmar Employment or leadership position: Genentech Stock ownership: Genentech Research funding: Genentech Y. Mun Employment or leadership position: Genentech/Roche Stock ownership: Genentech/Roche N. Yao Employment or leadership position: Genentech Stock ownership: Genentech, Gilead, AstraZeneca, GSK Other remuneration: leadership - Genentech J. M. Burke Consultant or advisory role: Adaptive Biotechnologies, AstraZeneca, BeiGene, Epizyme, Kura, Kymera, Morphosys, Nurix, Roche/Genentech, SeaGen, TG Therapeutics, Verastem, X4 Pharmaceuticals Other remuneration: speaker’s bureau - Bristol Myers Squibb, SeaGen