Date: 2017-05-30
Type of
information: Clinical trial authorisation
phase: 1-2
Announcement: clinical trial authorization
Company: Loxo Oncology (USA - CT)
Product: LOXO-195
Action
mechanism:
- kinase inhibitor/TRK inhibitor. LOXO-195 is an oral and selective investigational new drug in clinical development for the treatment of patients with cancers that have acquired resistance to initial TRK therapy such as larotrectinib. Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. Though drugs such as larotrectinib can induce durable responses in these patients, the cancer may eventually begin to grow again. Emerging data in the field of TRK inhibition suggest that this acquired resistance may emerge due to TRK kinase point mutations, such as those in the solvent front domain, xDFG domain, or gatekeeper region. LOXO-195 was designed to address anticipated mechanisms of acquired resistance in cancers exposed to a prior TRK inhibitor, including “solvent front” mutations (e.g. NTRK1 G595R, NTRK3 G623R), which are not well-addressed by existing investigational agents.
- LOXO-195 will be developed as a sequential treatment, to follow larotrectinib or another TRK inhibitor, to extend the total time of benefit from TRK inhibition.
Disease: cancers that have acquired resistance to initial TRK therapy
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details:
Latest
news:
- • On June 3, 2017, Loxo Oncology announced the online publication of a new research brief in Cancer Discovery outlining the preclinical rationale for LOXO-195 and clinical proof-of-concept data from the first two patients treated.
- The Cancer Discovery research brief provides early evidence that the sequential use of larotrectinib followed by LOXO-195 could extend the total duration of disease control for patients with TRK fusion cancers. An analogous paradigm has already been established for other oncogene-addicted tumors, such as those driven by androgen and estrogen signaling, EGFR mutations and ABL gene fusions. The brief describes the first two patients with TRK fusion cancers who responded to larotrectinib but later relapsed. An adult with colorectal cancer and a child with infantile fibrosarcoma were biopsied at the time of tumor progression and found to have a solvent front TRK mutation in the existing TRK fusion, which explained the diminished activity of larotrectinib. As no other treatment options exist to address TRK fusion solvent front mutations, Loxo Oncology, in collaboration with the U.S. FDA, enabled these patients to access LOXO-195 through emergency use Investigational New Drug applications (INDs). Both patients responded to LOXO-195, with minimal adverse events reported.
- • On May 30, 2017, Loxo Oncology announced that the FDA cleared the Investigational New Drug (IND) application for LOXO-195. LOXO-195 will initially be studied in a multi-center Phase 1/2 trial. The primary objective of the trial is to determine the maximum tolerated dose or recommended dose for further study. Key secondary objectives include measures of safety, pharmacokinetics, and anti-tumor activity (i.e. Objective Response Rate and Duration of Response, as determined by RECIST v1.1). The trial will include a dose escalation phase and dose expansion phase.
Is
general: Yes
