Recently, the U.S. Food and Drug Administration (FDA) has issued regulatory decisions for agents to treat diffuse large B-cell lymphoma (DLBCL), small cell lung cancer (SCLC), acute myeloid leukemia (AML), biliary tract cancer, and graft-vs-host disease.
Priority Review for Loncastuximab Tesirine in Relapsed or Refractory DLBCL
The FDA accepted a biologics license application for loncastuximab tesirine in relapsed or refractory DLBCL and granted Priority Review status. The FDA has set a Prescription Drug User Fee Act (PDUFA) target date of May 21, 2021.
Loncastuximab tesirine (formerly ADCT-402) is an antibody-drug conjugate composed of a humanized monoclonal antibody directed against human CD19 and conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Once bound to a CD19-expressing cell, loncastuximab tesirine is designed to be internalized by the cell, following which the warhead is released.
The warhead is designed to bind irreversibly to DNA to create highly potent interstrand cross-links that block DNA strand separation, thus disrupting essential DNA metabolic processes such as replication and ultimately resulting in cell death. CD19 is a clinically validated target for the treatment of B-cell malignancies.
The application is based on data from LOTIS 2, a phase II multicenter, open-label, single-arm clinical trial evaluating the efficacy and safety of loncastuximab tesirine in patients with relapsed or refractory DLBCL following two or more lines of prior therapy. In June 2020, maturing data from LOTIS 2 were presented at the virtual 25th Congress of the European Hematology Association (Abstract S233).
As of the cutoff date, loncastuximab tesirine demonstrated an overall response rate of 48.3% (70 of 145 patients) and a complete response rate of 24.1% (35 of 145 patients). The tolerability profile was manageable, with the most common grade ≥ 3 treatment-emergent adverse events in ≥ 10% of patients being neutropenia (25.5%, with low incidence of febrile neutropenia [3.4%]), thrombocytopenia (17.9%), gamma-glutamyltransferase increase (16.6%) and anemia (10.3%).
Data from subgroup analyses of LOTIS 2 will be presented in a poster at the upcoming 2020 American Society for Hematology (ASH) Annual Meeting.
Loncastuximab tesirine is also being evaluated in LOTIS 3, a phase I/II clinical trial in combination with ibrutinib in patients with relapsed or refractory DLBCL or mantle cell lymphoma, and LOTIS 5, a phase III confirmatory clinical trial in combination with rituximab in patients with relapsed or refractory DLBCL.
Fast Track Designation for Investigational Irinotecan Liposome Injection as a Second-Line Monotherapy for SCLC
The FDA granted Fast Track designation to an irinotecan liposome injection for patients with SCLC whose disease had progressed following a first-line platinum-based regimen. The agent is a topoisomerase 1 inhibitor.
The injection is currently approved in the United States and in Europe in combination with fluorouracil and leucovorin for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy.
An ongoing phase III randomized trial (RESILIENT) is being conducted to assess the efficacy and safety of investigational irinotecan liposome injection as a monotherapy for patient with SCLC who experience disease progression on or after a first-line platinum-based regimen.
Fast Track Designation for Eprenetapopt in TP53-Mutant AML
The FDA granted Fast Track designation to eprenetapopt in the treatment of patients with TP53-mutant AML. The Company previously received Breakthrough Therapy, Orphan Drug, and Fast Track designations for eprenetapopt in the treatment of patients with TP53-mutant myelodysplastic syndromes (MDS).
Eprenetapopt (also known as APR-246) is a small molecule that has demonstrated reactivation of mutant and inactivated p53 protein by restoring wild-type p53 conformation and function, thereby inducing programmed cell death in human cancer cells. Preclinical antitumor activity has been observed with eprenetapopt in a variety of solid and hematologic cancers, including MDS, AML, and ovarian cancer, among others.
Additionally, strong synergy has been seen with both traditional anticancer agents, such as chemotherapy, as well as newer mechanism-based anticancer drugs and immuno-oncology checkpoint inhibitors. In addition to preclinical testing, a phase I/II clinical program with eprenetapopt has been completed, demonstrating a favorable safety profile and both biologic and confirmed clinical responses in hematologic malignancies and solid tumors with mutations in the TP53 gene.
Breakthrough Therapy Designation for Zanidatamab in Patients With Biliary Tract Cancer
The FDA granted Breakthrough Therapy designation to zanidatamab for patients with previously treated HER2 gene–amplified biliary tract cancer.
Zanidatamab is a bispecific antibody that can simultaneously bind two nonoverlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action, including dual HER2 signal blockade, increased binding, and removal of HER2 protein from the cell surface, and potent effector function leading to antitumor activity in patients.
This Breakthrough Therapy designation was based on an ongoing clinical trial of zanidatamab in patients with locally advanced, unresectable, and/or metastatic HER2-expressing tumors, including biliary tract cancer. Updated clinical data for single-agent zanidatamab in patients with biliary tract cancer has been accepted for presentation at the upcoming ASCO Virtual Gastrointestinal Cancers Symposium.
Zanidatamab is being developed in multiple phase I, phase II, and registration-enabling clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2.
Earlier this year, a global phase IIb registration-enabling study of single-agent zanidatamab in patients with previously treated HER2 gene-amplified biliary tract cancer was launched. This study, which is currently enrolling patients, is designed to support accelerated approval based on a primary endpoint of objective response rate, and secondary endpoints of duration of response and safety.
New Drug Application for Belumosudil in Patients With Chronic Graft-vs-Host Disease
The FDA has accepted a new drug application for belumosudil (KD025), a Rho-associated coiled-coil kinase 2 (ROCK2) inhibitor, for the treatment of patients with chronic graft-vs-host disease. The FDA granted Priority Review for the application, which provides for a 6-month review, and assigned a PDUFA target action date of May 30, 2021.
The FDA previously granted Breakthrough Therapy Designation to belumosudil for the treatment of patients with chronic graft-vs-host disease after failure of two or more lines of systemic therapy. The FDA also previously granted Orphan Drug designation to belumosudil for the treatment of chronic graft-vs-host disease.
Belumosudil is a selective oral inhibitor of ROCK2, a signaling pathway that modulates inflammatory response and profibrotic processes.
The FDA granted Breakthrough Therapy Designation to belumosudil for the treatment of patients with chronic graft-vs-host disease after failure of two or more lines of systemic therapy. The FDA also granted Orphan Drug Designation to belumosudil for the treatment of chronic graft-vs-host disease. The FDA granted Priority Review for the new drug application for belumosudil and assigned a PDUFA date of May 30, 2021.
The submission is supported by positive data from ROCKstar (KD025-213), a pivotal clinical trial evaluating belumosudil in patients with chronic graft-vs-host disease who have received two or more prior lines of systemic therapy.
ROCKstar (KD025-213) is an ongoing open-label trial of belumosudil in patients with chronic graft-vs-host disease who have received at least two prior lines of systemic therapy. Patients were randomly assigned to receive belumosudil at 200 mg once daily or 200 mg twice daily, enrolling 66 patients per arm. The primary endpoint of the study is overall response rate.
The overall response rate endpoint was met at the interim analysis, conducted 2 months after completion of enrollment. At the study’s primary analysis, conducted 6 months after completion of enrollment, belumosudil achieved overall response rates of 73% and 74% in the respective arms. Belumosudil has been well tolerated and adverse events have been consistent with those expected in the patient population.
Twelve-month data from ROCKstar will be presented in an oral session at the 2020 ASH Annual Meeting & Exposition.
New Drug Application for Infigratinib in Cholangiocarcinoma
The FDA accepted a new drug application for infigratinib, an oral FGFR1-3 selective inhibitor, for individuals with cholangiocarcinoma. The application has been granted Priority Review designation.
Infigratinib is an orally administered, ATP-competitive, FGFR1-3 tyrosine kinase inhibitor in development for the treatment of individuals with FGFR-driven conditions, including cholangiocarcinoma and urothelial carcinoma.
FDA Approves Device for Treatment of Osteoid Osteoma in the Extremities
On November 27, the FDA approved the Sonalleve MR-HIFU system for the treatment of osteoid osteoma in the extremities.
Magnetic resonance–guided high-intensity focused ultrasound (MR-HIFU) treatment is an image-guided technique combining high-intensity focused ultrasound ablation with real-time monitoring of temperature change during the sonication.
The clinical results support the probable benefit of Sonalleve MR-HIFU system for the ablation of painful osteoid osteoma. Efficacy was evaluated in a study of nine patients treated with MR-HIFU, without technical difficulties or serious adverse events. There was a statistically significant decrease in their pain scores within 4 weeks of treatment. No pain medication usage was achieved in eight of nine patients after 4 weeks.
For full information, including warnings and precautions, view the summary of safety and probable benefit document for the Sonalleve MR-HIFU system.
