Over the past few weeks, the U.S. Food and Drug Administration (FDA) granted reviews or designations to treatments for gastrointestinal cancers and lymphoma, and also provided authorizations for products designed to screen for malignancies and tumor mutational burden.
Priority Review for Nivolumab Plus Ipilimumab in Previously Treated Advanced Hepatocellular Carcinoma
The FDA accepted a supplemental biologics license application and granted Breakthrough Therapy designation for nivolumab in combination with ipilimumab for the treatment of patients with advanced hepatocellular carcinoma previously treated with sorafenib. The FDA granted the application Priority Review with a Prescription Drug User Fee Act (PDUFA) goal date of March 10, 2020.
This application is based on data from the nivolumab/ipilimumab cohort of the phase I/II CheckMate 040 study, an ongoing, open-label, multicohort study investigating nivolumab or nivolumab-based combinations in patients with advanced hepatocellular carcinoma with and without chronic viral hepatitis who are naive to, intolerant to, or who have had disease progression during sorafenib therapy. Data from this study were presented by Yau et al at the 2019 ASCO Annual Meeting (Abstract 4012).
Priority Review, Breakthrough Designation, Orphan Drug Designation for Pemigatinib in Cholangiocarcinoma
The FDA has accepted for Priority Review a new drug application for pemigatinib, a selective fibroblast growth factor receptor (FGFR) inhibitor, as a treatment for patients with previously treated, locally advanced, or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements; granted pemigatinib Breakthrough Therapy designation for the treatment of previously treated, advanced/metastatic, or unresectable FGFR2-translocated cholangiocarcinoma; and granted pemigatinib Orphan Drug designation for the treatment of cholangiocarcinoma. The PDUFA target action date is May 30, 2020.
Pemigatinib is a potent, selective, oral inhibitor of FGFR isoforms 1, 2, and 3. In preclinical studies, the drug has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations.
The new drug application submission is based on data from the FIGHT-202 study evaluating pemigatinib as a treatment for patients with previously treated, locally advanced, or metastatic cholangiocarcinoma. Study results—recently presented at the European Society for Medical Oncology Congress 2019 by Vogel et al—demonstrated that at a median follow-up of 15 months, in patients harboring FGFR2 fusions or rearrangements, pemigatinib monotherapy resulted in an overall response rate of 36% (the primary trial endpoint), and median duration of response of 7.5 months (the secondary endpoint). Adverse events were manageable and consistent with the mechanism of action of pemigatinib.
Fast Track Designation for TAC01-CD19 in DLBCL
The FDA granted Fast Track designation for TAC01-CD19 in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after at least two prior systemic therapies.
TAC01-CD19 is a novel T-cell therapy product targeting CD19, a validated target in lymphomas and leukemias. The product comprises patient-derived T cells that have been genetically engineered to express the CD19 T-cell antigen coupler (TAC). Preclinical data suggest that TAC01-CD19 has the potential for being highly efficacious with minimal side effects in hematological malignancies.
A phase I/II study (TACTIC-19) to be conducted in patients with CD19-positive B-cell malignancies, including DLBCL, is expected to be initiated by the end of 2019.
Orphan Drug Designation for TT-00420 in Cholangiocarcinoma
The FDA granted Orphan Drug designation to TT-00420, a clinical-stage investigational drug, for the treatment of cholangiocarcinoma.
TT-00420 is a novel, small-molecule, spectrum-selective multiple kinase inhibitor. A global, phase I, first-in-human trial is currently ongoing to evaluate the safety and tolerability of TT-00420 in patients with advanced solid tumors.
Orphan Drug Designation for Surufatinib in Pancreatic Neuroendocrine Tumors
The FDA granted Orphan Drug designation to surufatinib for the treatment of pancreatic neuroendocrine tumors.
Surufatinib (previously known as HMPL-012 or sulfatinib) is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptor and fibroblast growth factor receptor, which both inhibit angiogenesis, and colony-stimulating factor-1 receptor, which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be suitable for possible combinations with other immunotherapies. Surufatinib is in several late-stage and proof-of-concept clinical trials in China and proof-of-concept clinical trials in the United States.
Breakthrough Device Designation for Endoscopic AI System
AI Medical Service Inc, one of the world’s first real-time endoscopic artificial intelligence (AI) developers, has announced the company was granted Breakthrough Device designation by the FDA for its AI programs that analyze endoscopy images for potential diagnosis of gastric cancer.
AI Medical Service’s system applies neural network algorithms which are trained with large real-world datasets of images of biopsy-proven cancer lesions, benign lesions, and normal tissue that were captured using standard endoscopes, thus aiding physicians performing endoscopies to detect lesions suspicious for cancer. AI Medical's technology is further differentiated as it is able to detect gastric, colorectal, and esophageal cancer, especially for concurrent usage, whereas other entities’ technology tends to focus only on colorectal cancer.
Marketing Authorization of Omics Core
The FDA has granted marketing authorization to Omics Core, the first whole-exome tumor-normal in vitro diagnostic that measures overall tumor mutational burden in cancer tissue.
The Omics Core assay is the nation’s first FDA-authorized, custom-targeted, whole-exome sequencing platform to report both overall tumor mutational burden in tumor specimens from 19,396 protein-coding genes (whole-exome) and somatic alterations (point mutations, small insertions, and deletions) in 468 cancer-relevant genes. It is a qualitative in vitro diagnostic test that uses targeted next-generation sequencing of formalin-fixed paraffin-embedded tumor tissue matched with normal specimens from patients with solid malignant neoplasms to detect tumor gene alterations in a broad multigene panel.
Tumor mutational burden is reported via two metrics: total number of somatic nonsynonymous exonic variants within the 19,396 genes (whole-exome) surveyed, and an estimate of mutation rate by counting all somatic, synonymous, and nonsynonymous variants detected in gene coding regions and dividing by the approximate size of the whole exome.
