The FDA has granted Priority Review to the newly accepted Biologics License Application for tafasitamab and lenalidomide for the treatment of relapsed/refractory diffuse large B-cell lymphoma. The Prescription Drug User Fee Act target action date was set as August 30, 2020, with no plans for an advisory committee meeting to discuss the application.
The FDA has granted Priority Review to the newly accepted Biologics License Application (BLA) for tafasitamab and lenalidomide for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The Prescription Drug User Fee Act (PDUFA) target action date was set as August 30, 2020, with no plans for an advisory committee meeting to discuss the application.1
The BLA was submitted based on data from the phase II L-MIND trial, which is evaluating the efficacy and safety of tafasitamab plus lenalidomide in this patient population, as well as the observational retrospective cohort study (RE-MIND), which is evaluating lenalidomide monotherapy to set up a historical control for a clinical trial evaluating tafasitamab.
In the L-MIND trial, 81 patients were recruited. Twenty-three percent had early relapse defined as ≤12 months from diagnosis (n = 19), 40% were rituximab refractory (n = 34), and 42% were refractory to their last therapy. Twenty-six percent of patients had non-germinal center B cell-like (GCB) DLBCL (n = 21) and 49% had GCB DLBCL (n = 20). There were 42 patients who had an International Prognostic Index (IPI) of 3 to 5.2
The overall response rate (ORR) observed in the L-MIND trial was 58% per independent review committee, including a 33% complete response rate (CR) and a 35% partial response rate (PR), per investigator assessment. The ORR among patients with 2 or more prior therapies was 46%, 59% in those who were rituximab refractory, 56% among those who were refractory to their last treatment, 58% in patients with early relapse, 57% in patients who had baseline IPI of 3 to 5, 71% in patients with non-GCB DLBCL, and 53% in those with GCB-DLBCL.
The progression-free survival (PFS) rate was 16.2 months with tafasitamab (95% CI, 6.3-not reached [NR]) and was NR with lenalidomide (95% CI, 18.6-NR). From these data, Salles et al concluded that the combination demonstrated encouraging activity.
Seventeen percent of patients in the study experienced treatment-related serious adverse events, which were predominantly infection (10%), and neutropenic fever (5%).
L-MIND was a single-arm, open-label, multicenter study for which the primary end point was ORR. The secondary end points were disease control rate, duration of response, PFS, and the percentage of patients with overall survival. In the study, patients received tafasitamab 12 mg/kg via intravenous infusion weekly for cycles 1-3 then bi-weekly for cycle 4 onwards for 4-week cycles. Treatment with tafasitamab continued until disease progression, unacceptable toxicity, or discontinuation due to any other reason. Lenalidomide 25 mg was administered daily at 4-week cycles. Patients received up to 12 cycles of lenalidomide in the absence of disease progression or unacceptable toxicity.
The groundwork for the L-MIND trial was conducted in the RE-MIND study of 490 non-transplant eligible patients with response/refractory (r/r) DLBCL who were treated with lenalidomide monotherapy in the real-world setting throughout the United States and Europe.
The primary end point of the best overall ORR in RE-MIND was achieved in June of 2019. The ORR was 67.1% for the combination of tafasitamab and lenalidomide (95% CI, 55.4-77.5) compared with 34.2% (95% CI, 23.7-46.0) in the lenalidomide monotherapy group (P<.0001). There was ongoing superiority observed once the secondary end points of the study were assessed. Specifically, the CR rate in the combination arm was 39.5% compared with 11.8% in the monotherapy arm (P<.0001). There was also a significant difference in OS observed in the combination arm versus the monotherapy arm, which was not reached with versus 9.3 months, respectively (HR, 0.47; 95% CI, 0.30-0.73; P<.0008).3
Both the RE-MIND study and the L-MIND study are ongoing. Patients are actively being recruited for RE-MIND, with the target enrollment of 500 participants. L-MIND has reached its target enrollment of 81 participants. The prospective complete data for the RE-MIND and L-MIND trials are March 31, 2020, and November 2022.
The combination of tafasitamab and lenalidomide was granted Breakthrough Therapy Designation for r/r DLBCL in 2017. Tafasitamab, an anti-CD19 antibody is still investigational and the acceptance of the BLA for tafasitamab plus lenalidomide is a significant milestone for the agent.
"We are extremely pleased that the FDA has accepted filing of our application and granted priority review, as we believe that the combination of tafasitamab and lenalidomide may provide an additional treatment option for patients suffering from DLBCL, who have relapsed after or are refractory to the current standard of care," said Malte Peters, MD chief development officer of MorphoSys. "We would like to thank all patients participating in our clinical studies and we will continue to work relentlessly towards making tafasitamab available to patients."