SAN DIEGO, April 16, 2020 (GLOBE NEWSWIRE) -- Turning Point Therapeutics, Inc. TPTX, a precision oncology company developing next-generation therapies that target genetic drivers of cancer, today announced the publication of preclinical data and patient case studies from the Phase 1 portion of its TRIDENT-1 clinical study for its lead investigational drug, repotrectinib.
Among the findings published in the American Association of Cancer Research peer-reviewed journal, Clinical Cancer Research, repotrectinib demonstrated potent in vitro and in vivo activity in patient-derived preclinical models compared with proxy chemical compounds for other tyrosine kinase inhibitors (TKIs) against ROS1 and the ROS1 G2032R solvent-front mutation. The central nervous system (CNS) activity of repotrectinib was studied in an in vivo model and demonstrated significant reduction of metastatic brain lesions with longer survival compared to a proxy chemical compound for entrectinib.
"Our findings provide encouraging support for repotrectinib as a potential first-line treatment in ROS1-positive non-small cell lung cancer, and later-line use after progression from a prior ROS1 TKI," said Dr. Byoung Chul Cho, Division of Medical Oncology, Yonsei Cancer Center at Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea and corresponding author of the paper. "In addition, these preclinical data as presented initially at the annual AACR conference in 2019 and now expanded upon in the publication suggest repotrectinib may prevent or delay the emergence of the G2032R solvent-front mutation and subsequent compound mutations, potentially improving clinical outcomes."
In preclinical studies, repotrectinib potently inhibited in vitro and in vivo tumor growth and ROS1-downstream signaling in treatment-naïve models compared with proxy chemical compounds for crizotinib, ceritinib, and entrectinib. Compared to a lorlatinib proxy chemical compound in a xenograft model, repotrectinib markedly delayed the onset of tumor recurrence following drug withdrawal. In addition, repotrectinib induced anti-tumor activity in the CNS. Repotrectinib also showed selective and potent in vitro and in vivo activity against the ROS1 G2032R solvent-front mutation.
Patient case studies (from the previously reported July 22, 2019 data cut-off) included in the manuscript highlighted the potential for repotrectinib to prevent or delay ROS1 kinase domain resistance mutations.
"The emergence of resistance mutations and disease progression in the CNS are characteristics of ROS1-positive non-small cell lung cancer and represent a high unmet medical need given the lack of approved therapies," said Dr. Mohammad Hirmand, chief medical officer of Turning Point Therapeutics. "These findings highlighted in Clinical Cancer Research build on prior preclinical studies of repotrectinib and data we have shown from the Phase 1 portion of TRIDENT-1, and are encouraging for repotrectinib as a potential treatment for both TKI-naïve and -pretreated ROS1-positive non-small cell lung cancer patients."
Approximately 50 to 60 percent of crizotinib-resistant mutations are found within the ROS1 kinase, of which the ROS1 G2032R solvent-front mutation is the most common. In addition, it is estimated that approximately 50 percent of patients treated with ROS1-TKIs experience disease progression due to CNS metastases.
The Clinical Cancer Research article may be found online at https://clincancerres.aacrjournals.org/content/early/2020/04/08/1078-0432.CCR-19-2777
More information about the ongoing TRIDENT-1 study of repotrectinib may be found by searching clinical trial identifier NCT03093116 at https://clinicaltrials.gov.
About Turning Point Therapeutics Inc.
Turning Point Therapeutics is a clinical-stage precision oncology company with a pipeline of internally discovered investigational drugs designed to address key limitations of existing cancer therapies. The company's lead drug candidate, repotrectinib, is a next-generation kinase inhibitor targeting the ROS1 and TRK oncogenic drivers of non-small cell lung cancer and advanced solid tumors. Repotrectinib, which is currently being studied in a registrational Phase 2 study in adults and a Phase 1/2 study in pediatric patients, has shown antitumor activity and durable responses among kinase inhibitor treatment-naïve and pre-treated patients. The company's pipeline of drug candidates also includes TPX-0022, targeting MET, CSF1R and SRC, which is currently being studied in a Phase 1 trial of patients with advanced or metastatic solid tumors harboring genetic alterations in MET; TPX-0046, targeting RET and SRC, which is currently being studied in a Phase 1/2 trial of patients with advanced or metastatic solid tumors harboring genetic alterations in RET; and TPX-0131, a next-generation ALK inhibitor entering IND-enabling studies. Turning Point's next-generation kinase inhibitors are designed to bind to their targets with greater precision and affinity than existing therapies, with a novel, compact structure that has demonstrated an ability to potentially overcome treatment resistance common with other kinase inhibitors. The company is driven to develop therapies that mark a turning point for patients in their cancer treatment. For more information, visit www.tptherapeutics.com.
Forward Looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and therapeutic potential of Turning Point Therapeutics' drug candidate repotrectinib, and the results, conduct, and progress of Turning Point Therapeutics' TRIDENT-1 clinical study of repotrectinib. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as "plans", "will", "believes," "anticipates," "expects," "intends," "goal," "potential" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Turning Point Therapeutics' current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Turning Point Therapeutics' business in general, and the other risks described in Turning Point Therapeutics' filings with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Turning Point Therapeutics undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Contact:
Jim Mazzola
jim.mazzola@tptherapeutics.com
858-342-8272
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