DRP-104 for the Treatment of Non-Small Cell Lung Cancer
The FDA granted Fast Track Designation for the novel glutamine antagonist DRP-104 for the treatment of advanced, previously treated non-small cell lung cancer (NSCLC) patients whose tumors express mutations in KEAP1, NFE2L2, and/or STK11.
The single-agent activity of DRP-104 in both genetically modified and patient-derived xenograft mouse models of NSCLC with KEAP1 mutations was presented at the 2020 American Association for Cancer Research Annual Meeting. DRP-104 demonstrated consistent single-agent anti-tumor activity across a broad panel of models with different KEAP1 mutations.
The glutamine antagonist, DRP-104, is currently in early-stage clinical development. The mechanisms of action for DRP-104 include:
* direct irreversible inhibition of tumor cell addiction to glutamine leading to substantial single-agent activity and tumor regression;
* broad metabolic remodeling of the tumor microenvironment leading to enhanced anti-tumor immune activity; and
* stimulation of T effector, NK, and NKT cells and inhibition of immunosuppressive myeloid-derived suppressor cells and macrophage cells, leading to greater long-term durable responses and survival in animal models.
Orphan Drug Designation of Devimistat for Soft Tissue Sarcoma
The FDA granted Orphan Drug Designation for devimistat for the treatment of soft tissue sarcoma, which is a type of cancer that starts in the soft tissues of the body, such as fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues. There are more than 50 different types of soft tissue sarcomas, and clear cell is ranked among the rarest. A clinical trial will focus on the treatment of relapsed or refractory clear cell sarcoma.
Devimistat is a first-in-class clinical lead compound, which targets enzymes that are involved in cancer cell energy metabolism and are located in the mitochondria of cancer cells. It is designed to target the mitochondrial tricarboxylic acid (TCA) cycle, a process essential to tumor cell multiplication and survival, selectively in cancer cells.
Devimistat substantially increases the sensitivity of cancer cells to a diverse range of chemotherapeutic agents. This synergy allows for potential combinations of devimistat with lower doses of generally toxic drugs to be more effective with lower patient's side effects. Combination with devimistat represents a diverse range of opportunities to substantially improve patient's benefit in many different cancers.
The FDA has approved initiation of pivotal Phase III clinical trials in pancreatic cancer (AVENGER 500) and acute myeloid leukemia (ARMADA 2000), and has designated devimistat as an orphan drug for the treatment of pancreatic cancer, acute myeloid leukemia, myelodysplastic syndrome, peripheral T-cell lymphoma, and Burkitt lymphoma. The EMA has granted Orphan Drug Designation to devimistat for pancreatic cancer and acute myeloid leukemia.
First Companion Diagnostic Test for Expanded EGFR TKI Therapies in NSCLC
The FDA approved expanded claims for the cobas EGFR Mutation Test v2 as a companion diagnostic (CDx) for a broad group of therapies in the treatment of non-small cell lung cancer (NSCLC). This claim expansion allows the test to be used as a CDx for all five currently FDA-approved epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapies targeting EGFR mutations L858R and exon 19 deletions in accordance with the approved therapeutic product labeling. The group claim will also enable the test to be used as a CDx for any future-approved EGFR TKI therapies targeting the same mutations, without the need to conduct individual clinical studies with the test for each new therapy.
The cobas EGFR Mutation Test v2 is a real-time polymerase chain reaction (PCR) test for the qualitative detection of defined mutations of the EGFR gene in NSCLC patients. Defined EGFR mutations are detected using DNA isolated from formalin-fixed paraffin-embedded tumor tissue (FFPET) or circulating tumour DNA (ctDNA) from plasma derived from ethylenediaminetetraacetic acid (EDTA) anti-coagulated peripheral whole blood.