Recently, the U.S. Food and Drug Administration (FDA) granted Priority Review to therapies for pretreated patients with multiple myeloma and pediatric patients with ALK-positive anaplastic large cell lymphoma; granted Fast Track designation to novel agents in gastric/gastroesophageal junction cancer and triple-negative breast cancer; and issued a guidance on labeling recommendations for breast implants.
Priority Review for Anti-BCMA CAR T-Cell Therapy Idecabtagene Vicleucel for Pretreated Patients With Multiple Myeloma
The FDA accepted for Priority Review a biologics license application for idecabtagene vicleucel (ide-cel; also known as bb2121), an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell immunotherapy, for the treatment of adult patients with multiple myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. The FDA has set a Prescription Drug User Fee Act (PDUFA) goal date of March 27, 2021.
The application is based on results from the pivotal phase II KarMMa study, evaluating the efficacy and safety of ide-cel in 128 adults with heavily pretreated and highly refractory multiple myeloma exposed to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. Results from the study were shared during an oral presentation as part of the ASCO20 Virtual Scientific Program (Abstract 8503).
Priority Review for Crizotinib in Pediatric Patients With ALK-Positive Anaplastic Large Cell Lymphoma
The FDA accepted and granted Priority Review to a supplemental new drug application for crizotinib in the treatment of pediatric patients with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) that is anaplastic lymphoma kinase (ALK)-positive. Crizotinib received Breakthrough Therapy designation for the ALK-positive ALCL indication in May 2018 and, if approved, would be the first biomarker-driven therapy for this type of pediatric lymphoma. The PDUFA goal date for a decision by the FDA is January 2020.
Crizotinib is a tyrosine kinase inhibitor indicated for the treatment of patients with metastatic non–small cell lung cancer whose tumors are ALK-positive or ROS1-positive as detected by an FDA-approved test.
Anaplastic large cell lymphoma is a rare type of non-Hodgkin lymphoma, divided into ALK-positive or ALK-negative disease. Though the 5-year survival rate for children with cancer in the United States is now the highest it’s ever been (80%), children with cancer continue to face challenges in treating their disease, including rare tumor types, variations in medicine response, and prolonged risk of side effects.
The FDA submission is supported by the results from Study ADVL0912 and Study A8081013. Study ADVL0912 is a phase I/II study conducted in collaboration with the Children’s Oncology Group evaluating the maximum dose of crizotinib that is safe and tolerable, and assessing clinical activity in pediatric patients with relapsed or refractory solid tumors and ALCL. Study A8081013 evaluated crizotinib in pediatric and adult patients with advanced malignancies known to be ALK-positive other than non–small cell lung cancer and included patients with relapsed or refractory ALCL. These two studies showed antitumor activity in pediatric and adult patients who received crizotinib.
Fast Track Designation for DKN-01 in Gastric and Gastroesophageal Junction Cancer
The FDA granted Fast Track designation to DKN-01 for the treatment of patients with gastric and gastroesophageal junction adenocarcinoma whose tumors express high Dickkopf-1 protein (DKK1), following disease progression on or after prior fluoropyrimidine- and platinum-containing chemotherapy, and, if appropriate, HER2-targeted therapy.
DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of DKK1 protein, a modulator of Wnt/beta-catenin signaling. DKK1 has an important role in tumor cell signaling and in mediating an immunosuppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating natural killer ligands on tumor cells.
DKN-01 is currently being evaluated in clinical trials for gastroesophageal, gynecologic, hepatobiliary, and prostate cancers. In September 2020, the first patient was dosed in the DisTinGuish study of DKN-01 plus tislelizumab, an anti–PD-1 antibody, in patients with gastric or gastroesophageal junction cancer.
Fast Track Designation for Eganelisib in Combination With a Checkpoint Inhibitor and Chemotherapy for First-Line Treatment of Advanced Triple-Negative Breast Cancer
The FDA granted Fast Track designation to eganelisib (also known as IPI-549) in combination with a checkpoint inhibitor and chemotherapy for the treatment of patients with inoperable locally advanced or metastatic triple-negative breast cancer in the first-line setting.
Eganelisib is a first-in-class, oral immuno-oncology development candidate that selectively inhibits PI3K-gamma.
Patients are currently being enrolled into MARIO-3, an ongoing phase II study to evaluate eganelisib in a novel triple-combination front-line regimen with atezolizumab and paclitaxel in triple-negative breast cancer. The study is designed to enroll approximately 60 patients across two cohorts: approximately 30 patients with PD-L1–positive disease based on immunohistochemistry (IHC), and 30 patients with PD-L1–negative disease based on IHC.
The primary objective of the study is complete response as measured by Response Evaluation Criteria in Solid Tumors version 1.1, with assessments conducted through month 12. Secondary measures include objective response rate, time to complete remission, time to response, duration of complete response, duration of response, and progression-free survival.
FDA Issues Final Guidance on Certain Labeling Recommendations for Breast Implants
The FDA issued the final guidance, “Breast Implants - Certain Labeling Recommendations to Improve Patient Communication,” as part of the agency’s effort to help improve the information available to patients and health-care professionals about the risks of breast implants. The draft guidance of this document was issued in 2019.
“As new information has become available about the risks and complications of breast implants, it is critical that women have access to information they need to make informed decisions,” said Binita Ashar, MD, Director of the Office of Surgical and Infection Control Devices in the Center for Devices and Radiological Health. “After working with stakeholders, including patients, … we are recommending format and content changes to breast implant labeling so the information is presented in an easy-to-understand way. It is important that patients discuss the risks and benefits of breast implants with their health-care provider and we hope that these labeling recommendations will help in facilitating these discussions.”
Over the past several years, the FDA has received new information pertaining to risks associated with breast implants. These include breast implant–associated anaplastic large cell lymphoma, as well as systemic symptoms commonly referred to as breast implant illness that some patients attribute to their implants, which can include fatigue, “brain fog,” muscle or joint pain, and rash.
The FDA has taken a number of steps to better understand and address risks associated with breast implants, including convening the General and Plastic Surgery Devices Advisory Panel in 2019 to discuss the long-term benefits and risks of breast implants indicated for breast augmentation and reconstruction. The meeting covered a range of important topics on breast implant safety, including characterization of breast implant–associated anaplastic large cell lymphoma incidence and risk factors, as well as methods for assessing systemic symptoms.
The Panel issued recommendations on these topics, including that the FDA require a boxed warning in breast implant labeling and a standardized checklist as part of the informed consent process, revise the magnetic resonance imaging screening recommendations for silent ruptures of silicone gel–filled breast implants, and provide greater transparency regarding materials present in breast implants. The Panel also discussed the role of the patient device card in providing important information about the patient’s breast implant.
The final guidance provides recommendations for manufacturers to incorporate a boxed warning and a patient decision checklist into the labeling for breast implants to better ensure certain information is received and understood by patients. This guidance also recommends updated and additional labeling information, including updates to the silicone gel–filled breast implant rupture screening recommendations, inclusion of an easy-to-find description of materials, and provision of patient device cards that were recommended at the March 2019 Panel meeting. These labeling recommendations are intended to enhance, but not replace, discussions between doctors and patients about the benefits and risks of breast implants that relate to individual patients.
In addition to the current recommendations, the FDA has updated the guidance, “Saline, Silicone Gel, and Alternative Breast Implants,” to provide consistency with these labeling recommendations. The FDA will continue to work with professional medical societies, patient advocacy groups, and women’s health organizations to help ensure that risk information about these devices is disseminated to patients.
