Over the past week, the U.S. Food and Drug Administration (FDA) granted Priority Review to a combination therapy in diffuse large B-cell lymphoma (DLBCL); gave Fast Track designations for treatments in T-cell lymphoma and adenoid cystic carcinoma; granted Orphan Drug designation to an agent for the treatment of follicular lymphoma; accepted a biologics license application for a proposed biosimilar to bevacizumab; and assigned Breakthrough Device designation to the Elecsys GALAD score for the detection of liver cancer.
Priority Review for Tafasitamab and Lenalidomide in Relapsed or Refractory DLBCL
The FDA has accepted a biologics license application (BLA) and granted Priority Review to tafasitamab, an investigational anti-CD19 antibody, in combination with lenalidomide for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The agency has set a Prescription Drug User Fee Act goal date of August 30, 2020.
The BLA submission is based on primary analysis data from the L-MIND trial of tafasitamab in combination with lenalidomide in patients with relapsed or refractory DLBCL, and the retrospective observational matched control cohort Re-MIND evaluating efficacy outcomes of patients with relapsed or refractory DLBCL who received lenalidomide monotherapy.
The combination was granted Breakthrough Therapy designation by the FDA for the treatment of relapsed or refractory DLBCL in 2017.
L-MIND is a single-arm, open-label phase II study investigating the combination of tafasitamab and lenalidomide in patients with relapsed or refractory DLBCL after up to two prior lines of therapy, including an anti-CD20 targeting therapy, who are not eligible for high-dose chemotherapy and subsequent autologous stem cell transplantation. The study’s primary endpoint is objective response rate; secondary outcome measures include duration of response, progression-free survival, and overall survival.
In May 2019, the L-MIND study reached its primary completion. Primary analysis data with a cut-off date of November 30, 2018, included 80 patients enrolled into the trial who had received tafasitamab and lenalidomide and had undergone follow-up as per protocol for at least 1 year. Efficacy results in this update were based on response rates assessed by an independent review committee for all 80 patients.
Re-MIND, an observational retrospective study, was designed to isolate the contribution of tafasitamab in the combination with lenalidomide and to prove the combinatorial effect. The study compares real-world response data of patients with relapsed or refractory DLBCL who received lenalidomide monotherapy with the efficacy outcomes of the tafasitamab/lenalidomide combination, as investigated in the L-MIND trial. Re-MIND collected the efficacy data from 490 patients with relapsed or refractory DLBCL in the United States and European Union.
Qualification criteria for matching patients of both studies were prespecified. As a result, 76 eligible Re-MIND patients were identified and matched 1:1 to 76 of 80 L-MIND patients based on important baseline characteristics. Objective response rates were validated based on this subset of 76 patients in Re-MIND and L-MIND, respectively. The primary endpoint of Re-MIND has been met and shows a statistically significant superior best objective response rate of the tafasitamab/lenalidomide combination compared to lenalidomide monotherapy.
Fast Track Designation for Tipifarnib in T-Cell Lymphomas
The FDA granted Fast Track designation to tipifarnib for the treatment of adult patients with relapsed or refractory angioimmunoblastic T-cell lymphoma, follicular T-cell lymphoma, and nodal peripheral T-cell lymphoma with T follicular helper phenotype. Tipifarnib is a potent selective farnesyl transferase inhibitor.
In December 2019, data presented by Witzig et al at the 2019 American Society of Hematology Annual Meeting & Exposition showed durable clinical activity with tipifarnib as a monotherapy in relapsed or refractory angioimmunoblastic T-cell lymphoma. The data demonstrated an objective response rate of approximately 50% in a heavily pretreated patient population, with a median of three prior regimens. Additionally, enhanced antitumor activity was observed in patients who carried mutations in the killer-cell immunoglobulin-like receptor, a CXCL pathway-associated biomarker. These patients had an objective response rate of 70% and a complete response rate of 40%.
Fast Track Designation for AL101 in Recurrent or Metastatic Adenoid Cystic Carcinoma
The FDA granted Fast Track designation to AL101 for the treatment of recurrent or metastatic adenoid cystic carcinoma.
AL101 is a potent, selective, injectable small molecule gamma secretase inhibitor and was granted Orphan Drug designation in May 2019 for the treatment of adenoid cystic carcinoma. It is designed to potently and selectively inhibit Notch-1, -2, -3, and -4 receptors and is currently being evaluated in the phase II ACCURACY trial.
Orphan Drug Designation for Umbralisib in Follicular Lymphoma
The FDA granted Orphan Drug designation to umbralisib, an investigational dual inhibitor of PI3K-delta and CK1-epsilon, for the treatment of patients with follicular lymphoma.
Umbralisib is being evaluated across several types of lymphoma in the UNITY-NHL phase IIb registration-directed clinical trial. The follicular lymphoma cohort of the UNITY-NHL trial is designed to evaluate the safety and efficacy of umbralisib in patients with follicular lymphoma who have received at least two prior lines of therapy, including an anti-CD20 monoclonal antibody and an alkylating agent. In October 2019, the follicular lymphoma cohort met the primary endpoint of overall response rate.
The FDA has previously granted Orphan Drug designation to umbralisib for the treatment of patients with all three types of marginal zone lymphoma.
Biologics License Application Accepted for Proposed Biosimilar Bevacizumab
The FDA accepted a BLA for MYL-1402O, a proposed biosimilar to bevacizumab, for review under the 351(k) pathway. The FDA goal date set under the Biosimilar User Fee Act is December 27, 2020.
The BLA seeks approval of bevacizumab for the first- and second-line treatment of patients with metastatic colorectal cancer in combination with fluorouracil-based chemotherapy; first-line use for patients with nonsquamous non–small cell lung cancer; recurrent glioblastoma; metastatic renal cell carcinoma in combination with interferon alfa; and persistent, recurrent, or metastatic cervical cancer.
The BLA is supported by a global randomized, controlled phase III clinical trial that evaluated the efficacy, safety, and immunogenicity of proposed biosimilar vs bevacizumab. The study included patients diagnosed with stage IV nonsquamous non–small cell lung cancer. Eligible patients were randomly assigned to receive either the proposed biosimilar or bevcizumab, along with carboplatin and paclitaxel, for up to six cycles (18 weeks), after which the patients continued to receive monotherapy until week 42. Additionally, patients benefiting from the treatment continued on bevacizumab monotherapy. The primary endpoint was overall response at week 18. Secondary endpoints included safety, progression-free survival, and overall survival at weeks 18 and 42.
A total of 671 patients were enrolled. At week 18, the study met its primary endpoint, and the 90% confidence interval for the best objective response rate ratio was within the prespecified equivalence margin. Safety, which included immunogenicity, was found to be similar to bevacizumab.
Breakthrough Device Designation for GALAD Score to Support Earlier Diagnosis of Hepatocellular Carcinoma
The FDA granted Breakthrough Device designation to the Elecsys GALAD score. This algorithmic score combines sex and age with the biomarker results of the Elecsys AFP, AFP-L3, and PIVKA-II, and is intended to aid diagnosis of early-stage hepatocellular carcinoma.
The Elecsys GALAD score will be the first GALAD score, with regulatory approval, for use in in vitro diagnostics. Combined with ultrasound, the Elecsys GALAD score has the potential to support clinicians by giving them more accurate information at an earlier stage, thus improving patient outcomes while being minimally invasive and potentially also more affordable to health-care systems.
The GALAD score is a serum biomarker-based model that predicts the probability of having hepatocellular carcinoma in patients with chronic liver disease.
