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Context Mosun, a full-length, humanized, IgG1 CD20×CD3 bispecific antibody, demonstrated efficacy/safety in relapsed/refractory DLBCL (NCT02500407; Schuster, et al. ASH 2019). The phase I/II multicenter GO40554 (NCT03677154) study showed similar results for elderly/unfit patients with first-line DLBCL intolerant of full-dose chemoimmunotherapy (CIT) (Olszewski, et al. ASH 2020). Objective To describe updated GO40554 study data. Methods Two safety-evaluation cohorts were assessed (Mosun 13.5 mg and 30 mg), then a 30 mg expansion phase. Patients were aged ≥80 years; 60–79 years with impairment in ≥1 activity of daily living (ADL); instrumental ADL; or impaired cardiac, renal, or liver function. Patients received optional pre-treatment with prednisone (+/– vincristine), then intravenous mosun in step-up doses on days (D)1 (1 mg), 8 (2 mg), and 15 (full-dose: 13.5/30 mg) of cycle (C)1, and full (C1D15) dose on D1 of each 21-day cycle for eight cycles, continuing for ≤17 cycles. Results As of January 15, 2021, 40 patients received mosun (13.5 mg safety cohort, n=8; 30 mg safety cohort, n=7; 30 mg expansion, n=25). Median age: 84 (range 67–100) years; 50% with Ann Arbor Stage III–IV, 80% with IPI score ≥2. Of 40 treated patients, 27 (67.5%) had ≥1 mosun-related adverse event (AE); 15 (37.5%) had a grade 3–4 AE. Most common treatment-emergent AE: cytokine release syndrome (CRS; n=9, 22.5%); five patients had neutropenia (12.5%). Six (15%) patients had grade 1 CRS per ASTCT (Lee, et al. Biol Blood Marrow Transplant 2019); three (7.5%) had grade 2 CRS, all managed with supportive care, fluids for hypotension, steroids, or low-flow oxygen, as required (no tocilizumab, vasopressors, high-flow oxygen, or intensive care). 14 (35%) patients discontinued due to progressive disease (PD). Overall response rate for efficacy-evaluable patients (n=31): 67.7%; complete response (CR) rate: 41.9%. Responses with 13.5 mg mosun: CR: 37.5%; PR: 37.5%; PD: 25%; with 30 mg mosun: CR: 43.5%; PR: 21.7%; stable disease/PD: 34.8%. Four durable responses were observed ≥12 months from start of therapy in 13 patients with CR (11 ongoing). Conclusions Mosun showed promising efficacy, including durable responses, and tolerable safety for elderly/unfit patients with 1L DLBCL; it should be further evaluated as a chemotherapy-free backbone for patients unable to tolerate standard CIT. |
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