FDA Pipeline: Fast Track Designation in Myelodysplastic Syndrome and AML, Plus Multiple Breakthrough Designations

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Recently, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to magrolimab in myelodysplastic syndrome and acute myeloid leukemia (AML). The agency also granted Breakthrough Therapy designations in lung cancer and desmoid tumors, as well as Breakthrough Device designations for colon and liver cancer detection.

Fast Track Designation for Magrolimab

The FDA has granted Fast Track designation to magrolimab (formerly known as 5F9) for the treatment of myelodysplastic syndrome and acute myeloid leukemia (AML). Magrolimab is a monoclonal antibody against CD47 that is designed to interfere with the recognition of CD47 by the SIRPα receptor on macrophages, thus blocking the “don't eat me” signal used by cancer cells to avoid being ingested by macrophages.

Magrolimab has been granted Fast Track designation by the FDA for the treatment of relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. Magrolimab has also been granted Orphan Drug designation by the FDA and the European Medicines Agency for the treatment of AML.

Breakthrough Therapy Designation for Capmatinib

The FDA has granted Breakthrough Therapy designation to capmatinib as a first-line treatment for patients with metastatic MET exon14 skipping–mutated non–small cell lung cancer (NSCLC). Recent research concluded that the cMET gene is an oncogenic driver, and capmatinib has been shown to be a highly potent and selective MET inhibitor. The MET mutation is seen in an estimated 3% to 4% of all patients with NSCLC. These patients are generally older and often have a poor prognosis that can limit lung cancer treatment options.

The FDA granted Breakthrough Therapy designation for capmatinib based on positive primary results from the GEOMETRY mono-1 study presented at the 2019 ASCO Annual Meeting (Abstract 9004).

Breakthrough Therapy Designation for Nirogacestat

The FDA has granted Breakthrough Therapy designation to nirogacestat, an oral, selective, small-molecule gamma-secretase inhibitor, for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis. The designation was based on phase I and phase II data evaluating nirogacestat as a monotherapy in patients with desmoid tumors.

Nirogacestat has been investigated in 24 patients with desmoid tumors across phase I and II clinical trials. In these studies, treatment with nirogacestat demonstrated a 100% disease control rate as measured by Response Evaluation Criteria in Solid Tumors, and median progression-free survival was not reached by the time of publication in either trial due to a lack of patients showing disease progression on therapy. Nirogacestat was generally well tolerated in these studies, with many patients remaining on treatment for years and only one patient with a desmoid tumor in the combined trials discontinuing treatment due to an adverse event. The most common adverse events in the phase II study were diarrhea, skin disorders, and hypophosphatemia.

Previously, the FDA had granted nirogacestat Orphan Drug designation for the treatment of desmoid tumors in June 2018 and Fast Track designation for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis in November 2018.

Breakthrough Device Designation for the LifeKit Prevent Test

The FDA granted Breakthrough Device designation to the LifeKit Prevent Colorectal Neoplasia Test. This is the first designation for a noninvasive diagnostic test that is designed to detect precancerous polyps, as well as early-stage carcinomas, with the potential to aid in the interception of carcinogenesis and prevention of colorectal cancer. Other noninvasive tests on the market primarily detect existent cancer, not precancerous adenomas, and require programs that rely heavily on colonoscopies to achieve colon cancer prevention.

The LifeKit Prevent Test deploys patented metagenomics technologies intended to identify microbial DNA and RNA biomarkers that are associated with neoplasia in the lower gastrointestinal tract. Using a noninvasive collection swab, the microbial biomarkers in the stool are analyzed. A positive result indicates the presence of colorectal adenomas or colorectal cancer, which should be followed by a diagnostic colonoscopy and polypectomy as appropriate.

Breakthrough Device Designation for Liquid Biopsy Liver Cancer Detection Test

The FDA granted Breakthrough Device designation to the Laboratory for Advanced Medicine’s liver cancer detection test. The liquid biopsy blood test is designed to detect the presence of liver cancer as early as stage I disease, with high specificity and sensitivity.

The Laboratory for Advanced Medicine previously reported data from the preliminary clinical study of its cfDNA methylation–based biomarkers for the noninvasive detection of hepatocellular carcinoma, demonstrating 95% sensitivity and 97.5% specificity. The data were presented at the Society for Immunotherapy of Cancer 33rd Annual Meeting in November 2018 (Abstract P125) and at the American Association for Cancer Research Annual Meeting in March 2019.

Subjects with a diagnosis of liver cirrhosis and who are currently recommended for hepatocellular carcinoma screening every 6 months by ultrasound are being enrolled in the CLiMB trial during a routine screening visit. Within the same clinical visit as the ultrasound, blood samples are being drawn for the liver cancer test and to determine the concentration of blood analytes. Samples for the liver cancer test will be collected using the collection kit, according to the instructions provided with each sample collection kit and shipped to a laboratory for processing and testing. The anticipated study duration for most subjects is approximately 1 month to complete one round of hepatocellular carcinoma screening using the liver cancer test, ultrasound, and diagnostic imaging.

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®.