Safety of Subcutaneous Mosunetuzumab in Refractory B-Cell Lymphomas: Trial Results

Mosunetuzumab (Mosun), a CD20xCD3 T- cell engaging bispecific monoclonal antibody(Bi-mAb), is the first Bi-mAb of its kind to be approved for the treatment of regressed or refractory follicular carcinoma. It’s administered intravenously and has a fixed treatment duration, making it accessible for inpatient use. A subcutaneous( SC) expression is being evaluated to ameliorate safety and convenience further. The results of a larger population with longer follow-up than preliminarily reported( Bartlett et al., ASH 2021) are presented then.

The Phase I and II, open-marker, multicenter cure-escalation and expansion study( GO29781; NCT02500407) included cases with regressed or refractory B- cell non-Hodgkin carcinoma( R/ R B- NHL). Cure- escalation groups entered Mosun 5 mg on Cycle( C) 1, Day( D) 1, 15 mg or 45 mg on C1D8, and 45 mg on C1D15 and D1 from C2 onwards( 5/ 15/ 45 mg( Group 1) and 5/ 45/ 45 mg( Group 2), independently). A third group entered Mosun 5 mg on C1D1, 45 mg on C1D8, 90 mg on C1D15 and C2D1, and 45 mg on D1 from C3 onwards(5/45/90/ 90/ 45 mg( Group 3)). Cases with a complete response( CR) after eight cycles completed treatment, while those with partial response or stable complaint progressed with remedy until 17 cycles.

At the data cut-off ( May 20, 2022), 89 cases with R/R B- NHL had entered SC Mosun( Group 1 n = 39, Group 2 n = 47, Group 3 n = 3). The most common histologies were verbose large B- cell carcinoma( 56), converted FL( 19), and FL( 12), with a median age of 68 times( 24 – 88) and a median number of previous systemic curatives at 3.85.1 and83.9 of cases were refractory to their last original remedy or previous anti-CD20 treatment, independently;32.6 had entered previous Auto T- cell remedy. The median time on study was9.9 months( m;0.4 –19.7), and the median cycles completed was 5( 1 – 17). No cure-limiting venom was observed in cure escalation. The most common- Grade( Gr) adverse events( AEs) were injection-point response( 62 all Gr1/2) and cytokine release pattern( CRS; 27; all Gr1/2). Grade 3/4 and serious AEs were reported in 49 and 45 pts independently. One AE led to Mosun’s termination(COVID-19; Group 1).

Grade 5 AEs were reported in 5 pts; none were considered Mosun- related by investigators( Group 1 n = 3( COVID- 19 n = 2; large intestine perforation n = 1); Group 2 n = 2( COVID- 19 pneumonia and septic shock)). CRS has been reported in 15/39 pts ( 38),8/47 pts( 17), and 1/3 pts in Groups 1, 2, and 3 independently. Utmost CRS events passed during C1. Median onset time since the previous Mosun and median duration was two days( ranges 0 – 4 and 1 – 6, independently).

The overall response rate was 82 in idle NHL( all FL;11/11) and 36 in aggressive NHL( aNHL); the CR rate was 64 in iNHL and 20 in aNHL, with18/22 CRs( 82) ongoing at data cut- off. The median duration of response was 6.7 m( 95 CI4.8 – not estimable) in aNHL and not reached in iNHL( 9- m event-free rate 78( 95 CI 51 – 100)).

Source:https://ash.confex.com/ash/2022/webprogram/Paper157729.html

Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT02500407

Budde, E., Bartlett N., Giri P, Schuster S, Assoulines S, Yoon S, Fay K, Matasar M, Gutierrez N, Marlton P, Dreyling M, Yoon D, Hess G, Radford J, Wiebking V, Yin S, Cybulski E, Turner D, Huang H, Zhou M, Penuel E, Wei M, and Shen L (2022). Subcutaneous Mosunetuzumab Is Active with a Manageable Safety Profile in Patients (pts) with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin Lymphomas (B-NHLs): Updated Results from a Phase I/II Study. [online] ash.confex.com. Available at: https://ash.confex.com/ash/2022/webprogram/Paper157729.html [Accessed 20 Feb. 2023].