Recently, the U.S. Food and Drug Administration (FDA) approved the first liquid biopsy companion diagnostic that also uses next-generation sequencing technology to identify patients with non–small cell lung cancer (NSCLC) and specific types of EGFR mutations. The FDA also granted Fast Track designations to agents for ovarian cancer and acute myeloid leukemia and has accepted for review a new drug application for a treatment for marginal zone and follicular lymphomas.
Approval for the First Liquid Biopsy Next-Generation Sequencing Companion Diagnostic Test
The FDA has approved the first liquid biopsy companion diagnostic that also uses next-generation sequencing technology to identify patients with NSCLC and specific types of EGFR mutations. This is the first approval to combine two technologies—next-generation sequencing and liquid biopsy—in one diagnostic test in order to guide treatment decisions.
“Approval of a companion diagnostic that uses a liquid biopsy and leverages next-generation sequencing marks a new era for mutation testing,” said Tim Stenzel, MD, PhD, Director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health. “In addition to benefiting from less invasive testing, patients are provided with a simultaneous mapping of multiple biomarkers of genomic alterations, rather than one biomarker at a time, which can translate to decreased wait times for starting treatment and provide insight into possible resistance mechanisms.”
The Guardant360 CDx assay utilizes two technologies. The first, liquid biopsy, uses a blood sample to provide health-care professionals with genetic information about the patient’s tumor. It is less invasive and more easily repeatable in comparison to standard tissue biopsies. Furthermore, liquid biopsy tests can be used in cases in which standard tissue biopsies are not feasible, for instance, due to the location of the tumor.
The second technology is next-generation sequencing, which uses large-panel genetic sequencing known as high-throughput tumor profiling. Compared to older technologies, next-generation sequencing requires only one test in order to allow clinicians better assessment of tumor composition, giving providers an advantage in evaluating which mutations are problematic. The Guardant360 CDx assay uses next-generation sequencing technology to simultaneously detect mutations in 55 tumor genes, rather than one gene at a time.
While the Guardant360CDx can provide information on multiple solid tumor biomarkers, this approval is specific to its use in identifying EGFR mutations in patients who will benefit from treatment with osimertinib, an FDA-approved therapy for a form of metastatic NSCLC. Genomic findings for other biomarkers evaluated are not validated for choosing a particular corresponding treatment with this approval. If the specific NSCLC mutations associated with this approval are not detected in the blood, then a tumor biopsy should be performed to determine if the NSCLC mutations are present.
Fast Track Designation for XMT-1536 in Platinum-Resistant Ovarian Cancer
The FDA granted Fast Track designation to XMT-1536 for the treatment of patients with platinum-resistant high-grade serous ovarian cancer who have received up to three prior lines of systemic therapy, or patients who have received four prior lines of systemic therapy, regardless of platinum status.
XMT-1536 is a first-in-class antibody-drug conjugate targeting the sodium-dependent phosphate transport protein NaPi2b. The NaPi2b antigen is broadly expressed in ovarian cancer and NSCLC. XMT-1536 is being studied in an ongoing phase I proof-of-concept clinical trial in patients with tumors expressing NaPi2b.
Fast Track Designation for Aspacytarabine in Acute Myeloid Leukemia
The FDA granted Fast Track designation for aspacytarabine (also known as BST-236) for the treatment of acute myeloid leukemia (AML) in adults aged 75 or older, or who have comorbidities that preclude the use of intensive induction chemotherapy.
Aspacytarabine is a novel antimetabolite designed to provide the benefit of intensive chemotherapy while avoiding much of its toxicity. It is composed of cytarabine covalently bound to asparagine, acting as a prodrug of cytarabine. Cytarabine has served as the backbone of AML therapy for over 40 years due to its superior efficacy; however, it is associated with severe bone marrow, gastrointestinal, and neurologic toxicities, which significantly limit its use, especially in older and medically compromised patients. Due to its unique kinetics and metabolism, aspacytarabine is designed to enable high-dose therapy with lower systemic exposure to free cytarabine and relative sparing of normal tissues.
A phase IIb study is evaluating aspacytarabine as a single-agent first-line AML therapy for patients unfit for standard chemotherapy. Initiation of a phase II trial of aspacytarabine in patients with relapsed or refractory myelodysplastic syndromes and AML is slated to begin in the fourth quarter of 2020.
New Drug Application for Umbralisib in Previously Treated Marginal Zone Lymphoma and Follicular Lymphoma
The FDA accepted a new drug application for umbralisib, an investigational once-daily, oral, dual inhibitor of PI3K-delta and CK1-epsilon, as a treatment for patients with previously treated marginal zone lymphoma who have received at least one prior anti-CD20 based regimen and follicular lymphoma who have received at least two prior systemic therapies. The marginal zone lymphoma indication, under Breakthrough Therapy designation, has been accepted for Priority Review and has a Prescription Drug User Fee Act (PDUFA) goal date of February 15, 2021. The follicular lymphoma indication has been accepted for standard review with a PDUFA goal date of June 15, 2021.
The new drug application for umbralisib was based primarily on data from the monotherapy marginal zone lymphoma and follicular lymphoma cohorts of the UNITY-NHL phase IIb trial. Each cohort met its primary endpoint of overall response rate, achieving the target guidance of 40% to 50% overall response rate, as confirmed by an independent review committee.
