Trial drugs

From Medullary Thyroid Cancer

Drugs in various FDA trials

  • LOXO Oncology - LOXO 292
    • LOXO-292 / Selpercatinib / Retevmo is an oral and selective investigational drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. Genomic alterations in the RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. RET fusions have been identified in approximately 2% of non-small cell lung cancer, 10-20% of papillary thyroid cancers, and a subset of other cancers. Activating RET point mutations account for approximately 60% of medullary thyroid cancer (MTC). Both RET fusion cancers and RET-mutant MTC are primarily dependent on a single activated kinase for their proliferation and survival. This dependency, often referred to as “oncogene addiction,” renders such tumors highly susceptible to small molecule inhibitors targeting RET. LOXO-292 was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach. LOXO-292 is currently being studied in the global LIBRETTO-001 Phase 1/2 trial.
  • Blueprint Medicines - BLU-667/Pralsetinib
    • The ARROW clinical trial will test an investigational drug called Pralsetinib (formerly known as BLU-667) in people who have RET-altered non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) or another solid tumor that has a RET fusion or mutation. It is a phase 1/2 trial designed to test the safety and the initial clinical activity of Pralsetinib.
  • Oncoceutics - ONC201
    • ONC201 is the first of a new group of cancer therapies called imipridones that have a novel mechanism of action. Unlike other oncology drugs, ONC201 and other imipridones selectively target G protein-coupled receptors (GPCRs) that are dysregulated in cancers.
ONC201 is an orally active dopamine receptor D2 (DRD2) antagonist that is well-tolerated and has been shown in Phase I and II clinical trials to be active in specific advanced cancers. Clinical trials of ONC201 in glioma patients with the H3 K27M mutation are underway at several locations in the U.S.
About 10% of adults with glioma have the H3 K27M mutation. About 50-60% of children with high-grade glioma (and 80-90% of children with Diffuse Intrinsic Pontine Gliomas, or DIPG) have the H3 K27M mutation. The test is commercially available and easily accessible either through immunohistochemistry (IHC) staining or gene sequencing.
  • Turning Point Theraputics - TPX-0046
    • TPX-0046 is a multi-targeted orally bioavailable TKI with a novel three dimensional macrocyclic structure that is being developed as a RET and SRC kinase inhibitor. TPX-0046 has the ability to demonstrate clinical activity in both treatment-naïve patients and in patients that develop solvent-front mutations.
TPX-0046 has completed IND-enabling studies and cleared its IND. During the 2H of 2019, we initiated a Phase 1/2 clinical trial of TPX-0046 for the treatment of advanced solid tumors with abnormal RET genes.
A Novel Approach to Target RET Signaling
A dual inhibitor of RET and SRC represents a novel therapeutic strategy to target abnormal RET signaling in cancers.
RET is a receptor tyrosine kinase, and constitutive activation of RET through mutations, amplifications and fusions have been found in multiple tumor types, including lung cancer, thyroid cancer and colon cancer. Importantly, the inhibition of the SRC kinase has the potential to reduce the recruitment of multiple receptor tyrosine kinases involved in bypass resistance and therefore increase the therapeutic effect seen with RET inhibitors. In addition, TPX-0046 does not inhibit VEGFR kinases, which are often associated with cardiovascular toxicities such as hypertension.