NP30179 phase I/II study: Fixed-duration glofitamab in R/R MCL

Patients with R/R MCL face a poor prognosis, and while CAR T-cell therapy and pirtobrutinib offer treatment options, their use is constrained by limited accessibility and durability of response. A phase I/II NP30179 trial (NCT03075696) evaluated the efficacy and safety of fixed-duration glofitamab monotherapy in patients with R/R MCL. Results were published in the Journal of Clinical Oncology by Phillips et al.

In total, 60 patients with R/R MCL and ≥1 previous line of therapy received obinutuzumab pretreatment (1,000 or 2,000 mg) 7 days before the first glofitamab dose. Glofitamab SUD was administered in Cycle 1 (Days 8 [2.5 mg] and 15 [10 mg]), with a Cycle 2 onward target dose of 16 mg or 30 mg Q3W for 12 cycles. Study outcomes included investigator-assessed CR rate and ORR, DoCR, DoR, PFS, OS, and safety. 

Key learnings

The investigator-assessed CR rate was 78.3%, with an ORR of 85.0%, a median DoCR of 15.4 months, and median DoR of 16.2 months. The median PFS and OS were 16.8 months and 29.9 months, respectively; 12-month PFS and OS were 56.7% and 73.9%, respectively. 

Patients previously treated with BTKi had lower response rates (CR: 71.0%, ORR: 74.2%) vs BTKi-naïve patients (CR: 86.2%, ORR: 96.6%).

All patients had ≥1 AE; the most common were CRS (70.0%), neutropenia (38.3%), COVID-19 (31.7%), and pyrexia (31.7%). Grade 3/4 AEs and SAEs occurred in 65.0% and 78.3% of patients, respectively. CRS was more frequent with obinutuzumab pretreatment 1,000 mg vs 2,000 mg (87.5% vs 63.6%). 

Results from the phase I/II NP30179 trial showed high CR rates, durable responses, and a manageable safety profile of fixed-duration glofitamab in patients with R/R MCL, including in BTKi-pretreated patients, supporting further evaluation in phase III trials.​