The FDA recently issued announcements on a Fast Track designation, a Priority Review, two supplemental new drug applications, an investigational new drug application, and a marketing clearance. The agency also released a safety communication on cancer-related surgery.
Fast Track Designation for LN-145 for Cervical Cancer
The FDA granted Fast Track designation for LN-145 for the treatment of patients with recurrent, metastatic, or persistent cervical cancer who have had disease progression while on or after chemotherapy. LN-145 is an adoptive cell therapy produced using tumor-infiltrating lymphocyte manufacturing technology.
Preliminary data from the phase II study of LN-145 for cervical cancer (C-145-04) was reported in October 2018 for 15 patients, yielding an overall response rate of 27%. Patients in the study had received a median of five prior therapies. The most common treatment-emergent adverse events included chills, pyrexia, and anemia.
The protocol for the cervical cancer study has since been amended to limit the number of prior therapies to no more than three and to exclude patients who have been treated with prior immunotherapy. The study is actively recruiting patients at 32 clinical sites in the United States and Europe.
Priority Review for Fedratinib in Myelofibrosis
The FDA accepted a new drug application and granted Priority Review for fedratinib. Fedratinib is a highly selective JAK2 inhibitor intended for the treatment of patients with myelofibrosis. The FDA has set its action date as September 3, 2019.
The NDA for fedratinib is based on results from a randomized, placebo-controlled, phase III trial (JAKARTA) in patients with primary or secondary myelofibrosis, as well as a single-arm, open-label phase II trial (JAKARTA2) in patients with primary or secondary myelofibrosis previously exposed to ruxolitinib, the only FDA-approved treatment for the disease. Results of these two trials have been previously published in peer-reviewed journals. The FDA has also provided fedratinib Orphan Drug designation for the treatment of secondary and primary myelofibrosis.
Researchers also plan to evaluate fedratinib in combination with luspatercept.
sNDA for Intravenous Use of Aprepitant for CINV
The FDA approved a supplemental new drug application (sNDA) for aprepitant injectable emulsion for intravenous (IV) use. The sNDA requested FDA approval to expand the administration of aprepitant beyond the already approved administration method (a 30-minute IV infusion) to include a 2-minute IV injection.
Aprepitant is the first and only polysorbate 80–free, IV formulation of a neurokinin 1 receptor antagonist indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Aprepitant and its prodrug, fosaprepitant, are the only single-agent neurokinin 1 receptor antagonists to significantly reduce CINV in both the acute phase (0–24 hours after chemotherapy) and the delayed phase (24–120 hours after chemotherapy).
Aprepitant was initially approved based on data demonstrating the bioequivalence of aprepitant to fosaprepitant, supporting its efficacy for the prevention of acute and delayed CINV following highly and moderately emetogenic chemotherapy. Results from two pivotal, randomized, crossover, bioequivalence studies of aprepitant and fosaprepitant showed subjects receiving aprepitant reported fewer adverse events than those receiving fosaprepitant, including substantially fewer infusion-site reactions. The new method of administration for aprepitant was approved based on a third study demonstrating bioequivalence and a comparable safety profile for aprepitant given as a 30-minute IV infusion and as a 2-minute IV injection.
sNDA for Lenalidomide in Combination With Rituximab in Follicular and Marginal Zone Lymphoma
The FDA granted Priority Review designation for the company’s supplemental new drug application (sNDA) for lenalidomide in combination with rituximab for the treatment of patients with previously treated follicular and marginal zone lymphoma. The FDA has set its action date as June 27, 2019.
The sNDA is based on results from the randomized, double-blind, phase III AUGMENT study, which evaluated the efficacy and safety of the investigational combination vs rituximab plus placebo in patients with relapsed/refractory follicular and marginal zone lymphoma. Results from the study were presented at the 2018 American Society of Hematology Annual Meeting & Exposition (Abstract 445).
Investigational New Drug Application for KO-539
The FDA cleared an investigational new drug application for KO-539, a potent and selective small-molecule inhibitor of the menin-mixed lineage leukemia (menin-MLL) protein-protein interaction. A phase I clinical trial of KO-539 in relapsed or refractory acute myeloid leukemia (AML) is anticipated in the second quarter of 2019.
MLL-rearranged leukemias are characterized by chromosomal translocations of the MLL gene that are primarily found in patients with AML and acute lymphoblastic leukemia (ALL. These translocations form oncogenes encoding MLL fusion proteins, which play a causative role in the onset, development, and progression of MLL-rearranged leukemias.
The target genes of the MLL fusion proteins are also found to be overexpressed in a broader subset of AMLs characterized by oncogenic driver mutations in genes such as NPM1. These mutations also appear to be dependent on the interaction between menin and MLL, suggesting that the menin-MLL complex is a central node in epigenetic dysregulation driven by distinct oncogenic driver mutations known to be important in AML and other hematologic malignancies.
In preclinical studies, KO-539 has demonstrated potent and selective inhibition of the proliferation of MLL-rearranged leukemia cell lines. Preclinical data also show robust and durable efficacy in multiple in vivo models of AML characterized by MLL rearrangements or oncogenic driver mutations in genes such as NPM1.
Market Clearance for Sculptura Radiation Oncology System
Sensus Healthcare, Inc, announced that the FDA has granted market clearance for the company’s Sculptura radiation oncology system. A single treatment during surgery, Sculptura can provide patients and physicians a single radiation treatment at the point of surgery.
Sculptura is a robotic intraoperative radiation therapy system that uses patented beam-sculpting capabilities to treat various cancers during surgery. The first Sculptura system has been installed at the University of Pennsylvania’s Perelman School of Medicine Department of Radiation Oncology.
Safety Communication on Using Robotically Assisted Surgical Devices for Cancer-Related Surgeries
On February 28, the FDA issued a safety communication to patients and health-care providers urging caution when using robotically assisted surgical devices for mastectomy and other cancer-related surgeries. Robotically assisted surgical devices enable surgeons to perform a variety of surgical procedures through small incisions in a patient’s body. Computer and software technology allow a surgeon to control surgical instruments attached to mechanical arms through small incisions, while viewing the surgical site in three-dimensional high definition. This type of surgery may help reduce pain, blood loss, scarring, infection, and recovery time after surgery in comparison to surgical procedures that do not use these devices.
The FDA has not granted marketing authorization for any robotically assisted surgical devices for use in mastectomy or for the treatment or prevention of cancer. However, the FDA is aware of scientific literature and media publications reporting poor outcomes for patients, including one limited report that describes a potentially lower rate of long-term survival when surgeons and hospital systems use robotically assisted surgical devices instead of traditional surgery for hysterectomy in cases of cervical cancer. In addition, the FDA has received a small number of medical device reports of patient injury when these devices are used in cancer-related procedures.
The safety communication warns patients and providers to be aware that the safety and effectiveness of robotically assisted surgical devices for mastectomy and any cancer-related surgery has not been established. In addition, the FDA urges health-care providers to complete the appropriate training for the specific robotically assisted surgical procedures performed.
The FDA also recommends that patients and health-care providers discuss the benefits, risks, and alternative procedure options to make informed treatment decisions. The agency also advises patients to ask their health-care providers about training, experience, and outcomes related to the use of robotically assisted surgery.
“[T]oday we are warning patients and providers that the use of robotically assisted surgical devices for any cancer-related surgery has not been granted marketing authorization by the agency, and therefore the survival benefits to patients when compared to traditional surgery have not been established,” said Terri Cornelison, MD, PhD, Assistant Director for the Health of Women in the FDA’s Center for Devices and Radiological Health. “Our surveillance using multiple tools—medical device reports, patient registries, scientific literature—helps us monitor and identify potential problems with medical devices as they arise. In the case of robotically assisted surgical devices and cancer-related uses such as mastectomy, we are aware of scientific literature reporting that surgeons have been using the device for uses not granted marketing authorization by the FDA. We want doctors and patients to be aware of the lack of evidence of safety and effectiveness for these uses so they can make better informed decisions about their cancer treatment and care. This safety communication issued today reflects the agency’s commitment to enhancing our oversight of device safety as part of our Medical Device Safety Action Plan, as well as the agency’s ongoing commitment to advancing women’s health.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.