"The transition to the new spray dried dispersion (SDD) formulation of glesatinib has succeeded in improving tolerability, resulting in significantly fewer formulation-specific side effects in patients with NSCLC. Early results with the SDD formulation have demonstrated promising activity in NSCLC patients with MET mutations," said
"We are similarly encouraged by data from our Phase 1b trial of sitravatinib, which indicate its potency in RET inhibition. Early results from the trial show clear evidence of tumor responses in NSCLC patients exhibiting RET fusion mutations."
Glesatinib Program Update
The SDD formulation of glesatinib was introduced into the Phase 1b trial and Phase 2 AMETHYST trial in May of 2016. This formulation has thus far demonstrated improved tolerability versus the prior miglyol soft gel formulation.
Patients from both Phase 1b and Phase 2 trials were assessed as of
In an initial evaluation of 24 genetically-selected patients treated with the SDD formulation of glesatinib:
In MET Exon 14 deletion patients treated with the SDD formulation across both the Phase 1b and Phase 2 trials, glesatinib demonstrated promising activity:
In MET amplification patients treated with the SDD formulation, glesatinib also demonstrated clinical benefit:
The Company expects to provide an additional update on the glesatinib program in the second half of 2017.
Sitravatinib Program Update
Sitravatinib is being evaluated in a Phase 1b expansion trial designed to evaluate its safety and efficacy in multiple pre-specified cohorts of cancer patients with genetic mutations involving sitravatinib targets, including a cohort of NSCLC patients with RET fusion mutations.
As of a data cut-off of
The Phase 1b trial is also enrolling NSCLC patients with CBL mutations, CHR4q12 amplification, and AXL alterations. As of the data cut-off date, no patients with these genetic mutations were evaluable.
Sitravatinib is also being evaluated in combination with nivolumab, a checkpoint inhibitor approved for the treatment of patients with a variety of solid tumors including NSCLC and metastatic renal cell carcinoma. Pre-clinical data indicate sitravatinib is an exceptionally potent inhibitor of the TAM (Tyro, Axl, Mer) and split (KDR, KIT) family tyrosine kinases which regulate multiple stages in the cancer immunity cycle and are thought to enhance anti-tumor immunity by improving the efficacy of checkpoint inhibitors (anti PD-1/PDL-1). The multicenter Phase 2 NSCLC trial enrolled its first patient in
The Company expects to provide an additional update on the sitravatinib program in Q3 2017.
Mocetinostat Program Update
A Phase 1b/2 trial combining mocetinostat, an orally administered spectrum-selective Class 1 HDAC inhibitor, and durvalumab, MedImmune's monoclonal antibody inhibiting PD-L1, continues to enroll patients with advanced solid tumors and NSCLC. The Company expects to provide an additional update on the mocetinostat program mid-year 2017.
Pre-Clinical Program Update
Two internally developed candidates are in pre-clinical development. The first is a highly-potent and potentially best-in-class LSD1 inhibitor with potential for rapid clinical proof-of-concept in small cell lung cancer or acute myeloid leukemia. An investigational new drug (IND) submission is planned for this compound in late 2017. Additionally, a mutant-selective KRAS inhibitor program is advancing to the candidate selection phase and prototype inhibitors have demonstrated marked tumor regression in KRAS mutant tumor models. An IND candidate selection is anticipated by the end of 2017.
About the glesatinib Phase 2 Trial ("AMETHYST")
AMETHYST is a multicenter, global Phase 2 trial designed to evaluate the safety and efficacy of glesatinib in NSCLC patients with MET genetic alterations who were previously treated with platinum-based chemotherapy and/or a checkpoint inhibitor. AMETHYST pre-specified patient cohorts include NSCLC with MET Exon 14 deletion and MET amplification. Enrollment rates in the AMETHYST trial have been supported by the Company's partnerships with molecular diagnostics companies providing commercially-available genetic testing, which have accelerated patient identification and enrollment.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release regarding the business of the Company that are not historical facts may be considered "forward-looking statements," including, but not limited to, statements regarding Mirati's development plans and timelines, the timing and potential future results of clinical trials, and the potential benefits of and markets for Mirati's product candidates. Forward-looking statements are typically, but not always, identified by the use of words such as "may," "would," "believe," "intend," "plan," "anticipate," "estimate," "expect," and other similar terminology. Forward-looking statements are based on current expectations of management and upon what management believes to be reasonable assumptions based on information currently available to it, and are subject to risks and uncertainties. Such risks and uncertainties may cause actual results to differ materially from the expectations set forth in the forward-looking statements. Such risks and uncertainties include, but are not limited to, potential delays in development timelines or negative clinical trial results, the fact that prior clinical or pre-clinical results may not be predictive of future results, reliance on third parties for development efforts, changes in the competitive landscape, changes in the standard of care, as well as other risks detailed in Mirati's recent filings on Forms 10-K and 10-Q with the United States Securities and Exchange Commission. Mirati undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances, or to reflect the occurrence of unanticipated events.
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