Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis

Objectives: To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity.Methods: In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infusion of placebo (n = 6) or MOR103 0.5 (n = 8), 1.0 (n = 8), or 2.0 (n = 9) mg/kg every 2 weeks for 10 weeks. Patients had to have ≤10 gadolinium (Gd)-enhancing brain lesions on T1-weighted MRI at baseline. The primary objective was safety.Results: Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The most frequent was nasopharyngitis. Between-group differences in TEAE numbers were small. There were no TEAE-related trial discontinuations, infusion-related reactions, or deaths. Nine patients experienced MS exacerbations: 3, 5, 1, and 0 patient(s) in the placebo, 0.5, 1.0, and 2.0 mg/kg groups, respectively. A few T1 Gd-enhancing lesions and/or new or enlarging T2 lesions indicative of inflammation were observed in all treatment groups. No clinically significant changes were observed in other clinical assessments or laboratory safety assessments. No anti-MOR103 antibodies were detected. PK evaluations indicated dose linearity with low/no drug accumulation over time.Conclusions: MOR103 was generally well-tolerated in patients with RRMS or SPMS. No evidence of immunogenicity was found.Classification of evidence: This phase 1b study provides Class I evidence that MOR103 has acceptable tolerability in patients with MS

Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma

Tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem-cell transplantation. To assess long-term outcomes, we report an updated analysis with ≥35 months' follow-up. Patients were aged >18 years, had received one to three prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was best objective response rate. After ≥35 months' follow-up (data cut-off: October 30, 2020), the objective response rate was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). The median duration of response was 43.9 months (95% confidence interval [95% CI]: 26.1-not reached), the median overall survival was 33.5 months (95% CI: 18.3-not reached) and the median progression-free survival was 11.6 months (95% CI: 6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most subgroups of patients. This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation. ClinicalTrials.gov identifier: NCT02399085

Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study

International audienc

Safety and efficacy of tafasitamab ± lenalidomide added to first-line R‑CHOP for DLBCL: Phase 1b First-MIND study.

Anti-CD19 immunotherapy tafasitamab in combination with lenalidomide is used in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplant. Open-label, phase 1b, First-MIND study assessed safety and preliminary efficacy of tafasitamab + R-CHOP ± lenalidomide as first-line therapy in patients with DLBCL. Adults with newly-diagnosed, untreated DLBCL (ECOG PS 0-2, IPI 2-5), were randomly assigned to R-CHOP+tafasitamab (Arm T) or R-CHOP+tafasitamab+lenalidomide (Arm T/L) for six cycles. Primary endpoint was safety; secondary endpoints included overall response rate (ORR) and complete response (CR) rate at end of treatment (EoT). From Dec2019-Aug2020, 83 patients were screened, 66 treated (n=33 per arm). All patients had ≥1 treatment-emergent adverse event, mostly grade 1/2. Grade ≥3 neutropenia and thrombocytopenia occurred in 57.6% and 12.1% of patients (Arm T), and 84.8% and 36.4% (Arm T/L). Non-hematologic toxicities occurred at similar rates between arms. Mean relative dose intensity of R-CHOP was 89% or higher in both arms. ORR at EoT was 75.8% (CR 72.7%) in Arm T and 81.8% (CR 66.7%) in Arm T/L; best ORR across visits was 90.0% and 93.9%. Eighteen-month duration of response and duration of CR rates were 72.7% and 74.5% (Arm T), and 78.7% and 86.5% (Arm T/L); 24-month progression-free survival and overall survival rates were 72.7% and 90.3% (Arm T), and 76.8% and 93.8% (Arm T/L). Manageable safety and promising signals of efficacy were observed in both arms. Potential benefit of adding tafasitamab+lenalidomide to R-CHOP is being investigated in phase 3 frontMIND (NCT04824092)

Long-term outcomes from the phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma

: Not available